The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index; 35 of the 65 sources its claims cite were checked for support.
E‐cadherin is essential for in vivo epidermal barrier function by regulating tight junctions
Open accessAbstract
Cadherin adhesion molecules are key determinants of morphogenesis and tissue architecture. Nevertheless, the molecular mechanisms responsible for the morphogenetic contributions of cadherins remain poorly understood in vivo. Besides supporting cell-cell adhesion, cadherins can affect a wide range of cellular functions that include activation of cell signalling pathways, regulation of the cytoskeleton and control of cell polarity. To determine the role of E-cadherin in stratified epithelium of the epidermis, we have conditionally inactivated its gene in mice. Here we show that loss of E-cadherin in the epidermis in vivo results in perinatal death of mice due to the inability to retain a functional epidermal water barrier. Absence of E-cadherin leads to improper localization of key tight junctional proteins, resulting in permeable tight junctions and thus altered epidermal resistance. In addition, both Rac and activated atypical PKC, crucial for tight junction formation, are mislocalized. Surprisingly, our results indicate that E-cadherin is specifically required for tight junction, but not desmosome, formation and this appears to involve signalling rather than cell contact formation.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Conditional loss of E-cadherin in mouse epidermis causes perinatal death from water loss due to impaired tight junction function, while desmosomes and cell-cell contacts remain largely intact. E-cadherin appears to regulate tight junction formation via signalling, involving mislocalization of activated aPKC and Rac rather than loss of adhesion per se.
Key findings
- K14-Cre/Ecad Fl/À mice died perinatally around 7–12 h after birth, lost about 9% body weight versus about 3% in controls, had increased haematocrit, and showed increased transepidermal water loss.
- The outside-in barrier remained functional, but inside-out permeability was impaired: biotin penetrated the granular layer to the stratum corneum, and epidermal resistance was three-fold lower in mutant skin than control skin, with dermal resistance not significantly affected (N=8 control, N=4 mutant; P=0.03).
- Tight junction components were mislocalized in mutant epidermis: claudin-1 was absent from the granular layer, claudin-4 showed punctate membrane distribution with less protein, and ZO-1 distribution was altered; occludin remained enriched at the membrane.
- Desmosomes formed normally and desmosomal cadherin expression was upregulated; P-cadherin was upregulated mainly in the basal layer. Activated aPKC was absent or largely diminished at suprabasal cell-cell borders, and Rac membrane localization was lost or diminished, while total activated Rac levels were unchanged.
Methods
- E-cadherin was conditionally inactivated in developing mouse epidermis using the Cre-loxP system with K14-Cre and floxed E-cadherin alleles, generating K14-Cre/Ecad Fl/Fl or K14-Cre/Ecad Fl/À mice; only data on K14-Cre/Ecad Fl/À mice are described because no phenotypic difference was found between lines.
- Analyses included RT-PCR, immunohistochemistry, Western blot, ultrastructural electron microscopy, weight and haematocrit measurements, TEWL measurement, lucifer yellow and toluidine blue penetration assays, intradermal biotin inside-out permeability assays, impedance analysis of skin biopsies, and Rac activation assays.
- Samples included newborn mice and embryonic stages E15.5, E16.5, and E18.5, depending on the assay.
Limitations
- The paper states that it remains unclear whether loss of E-cadherin impairs recruitment of activated aPKC to the membrane or whether aPKC is first recruited to adherens junctions and subsequently activated; it also notes that changes in activated Cdc42 may not be reflected by total Cdc42 levels.
- The paper states that the cornified layer may contribute to water loss in the mutants, although it is most likely not the primary cause.
- Evident from the text: many mechanistic conclusions are correlative and based on localization or protein-level changes rather than rescue experiments; impedance measurements used a small mutant sample (N=4); and only the K14-Cre/Ecad Fl/À line is described in the results.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
70 Own result · 40 Own interpretation · 21 No full text of the sources · 13 Supported · 10 Partly supported · 7 No basis given · 1 Supported so far · 1 Mixed support · 1 Sources not found · 1 Not checked yet · 1 Own method · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“As described previously (Young et al, 2003;Tinkle et al, 2004), no difference in localization of desmosomal markers like plakoglobin, desmocollin 2 and desmoglein 1/2 was observed (Figure 3A).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Cell-cell contacts are maintained in the absence of E-cadherin
What the sources say
- Partly supportedcites Young et al, 2003 sourceExperimental — accuracy not yet measured
The ‘Ablation of E-cadherin alters epidermal differentiation’ section (page not provided) says desmoglein expression was comparable in mutant and control tissue, and the Figure 6 caption reports similar localization of desmoplakin. The copy also reports preserved desmosomes, but it does not establish unchanged localization for plakoglobin or desmocollin 2, or specify desmoglein 1/2. (LLM, conf=0.86)
- Partly supportedcites Tinkle et al, 2004 sourceExperimental — accuracy not yet measured
The Results (Fig. 2 F and G; page not available) report largely similar plakoglobin levels in wild-type and E-cadherin knockout epidermis, but do not explicitly establish unchanged localization. The Results also report increased desmosomal cadherins by immunofluorescence in knockout spinous layers (Fig. 2 E), rather than an unchanged signal for desmogleins 1/2. Our copy does not report a comparison for desmocollin 2. (LLM, conf=0.82)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In control skin, biotin moves up to the stratum granulosum, where it is halted due to the presence of tight junctions, marked by occludin staining, between the cells of the granular layer (Furuse et al, 2002).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Increased permeability of tight junctions in the absence of E-cadherin
What the sources say
- Supportedcites Furuse et al, 2002 source
The Results section, under “Barrier functions of TJs in the epidermis” (Fig. 8), reports that in wild-type newborn mouse skin, the biotinylation reagent diffused to the second layer of the stratum granulosum and was stopped at occludin-positive tight junctions. The Discussion locates those junctions along the lateral membranes of granular cells. The claim accurately paraphrases this finding for control skin. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“These mice also have an apparently normal cornified envelope.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Increased permeability of tight junctions in the absence of E-cadherin
What the sources say
- Supportedcites Furuse et al, 2002 source
In Results, “Stratum corneum in claudin-1–deficient mice” (Fig. 9B), the authors report that cornified cell envelopes isolated from claudin-1–deficient epidermis were morphologically indistinguishable from those of wild-type epidermis. This directly supports the claim that they had an apparently normal cornified envelope. (LLM, conf=0.95)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Their importance in maintaining the epidermal barrier was underscored by the observations that in vivo inactivation of the tight junctional membrane protein claudin-1 results in epidermal water loss and ultimately in neonatal death of the mice (Furuse et al, 2002).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Introduction
What the sources say
- Supportedcites Furuse et al, 2002 source
The Results report that only claudin-1–deficient newborn mice showed excessive transepidermal water loss and that all homozygous mutants died within one day of birth. The Discussion reports both findings while noting that it could not conclusively establish whether dehydration caused death; the citing sentence attributes both outcomes to claudin-1 inactivation, not explicitly one to the other. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Like occludin, claudin-4 is found at the membrane in the granular layer of the epidermis in control mice (Furuse et al, 2002).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Increased permeability of tight junctions in the absence of E-cadherin
What the sources say
- Supportedcites Furuse et al, 2002 source
The Results section (Fig. 4B; page not supplied) reports claudin-4 in the second and third layers of the stratum granulosum of wild-type mice, concentrated at occludin-positive lines around granular cells. This supports its membrane localization in the granular layer of control mice. (LLM, conf=0.93)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Rac was found at the membrane in control mice, consistent with its function in cell-cell contact formation (Ehrlich et al, 2002).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Increased permeability of tight junctions in the absence of E-cadherin
What the sources say
- Partly supportedcites Ehrlich et al, 2002 sourceExperimental — accuracy not yet measured
The passage describing Figure 2A reports RacGFP accumulating along newly contacting membranes, supporting membrane localization during cell-cell contact formation. The Experimental Procedures describe cultured MDCK cells, not control mice; the source therefore does not support the claim's population or condition. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In vivo, claudin-1 is essential for the epidermal water barrier (Furuse et al, 2002).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > E-cadherin contributes to epidermal barrier formation by regulating the incorporation of claudins into tight junctions
What the sources say
- Supportedcites Furuse et al, 2002 source
The Discussion reports that claudin-1–deficient newborn mice had a severely impaired epidermal barrier and excessive transepidermal water loss. It concludes that epidermal claudin-1 is indispensable for creating and maintaining that barrier. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“A previous paper did not reveal a lethal phenotype around birth in mice in which E-cadherin was deleted in the epidermis using K14-Cre (Tinkle et al, 2004).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Epidermal E-cadherin is essential for water barrier formation
What the sources say
- Supportedcites Tinkle et al, 2004 source
The Results describe E-cadherin deletion in skin epithelium using K14-Cre and show newborn knockout pups. They also identify a full adult knockout mouse (Fig. 4), supporting the statement that the study did not reveal lethality around birth. Page numbers are unavailable in our copy. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“This paper, and another study, in which E-cadherin was inactivated in the epidermis after birth, showed a gradual loss of hair in the E-cadherin mutant mice (Young et al, 2003;Tinkle et al, 2004).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Epidermal E-cadherin is essential for water barrier formation
What the sources say
- Supportedcites Young et al, 2003 source
In “Ablation of E-cadherin in the epidermis and hair follicles of mutant mice” (page not provided), E-cadherin was reduced after birth in mutant mice, followed by progressive hair loss. The paper reports that loss became evident after 30 days and continued into adulthood. (LLM, conf=0.94)
- Supportedcites Tinkle et al, 2004 source
The Results report sparse hair in adult E-cadherin mutant mice and describe progressive loss of hair follicles with successive postnatal hair cycles. The phrase about inactivation after birth describes the other study, not necessarily this one. (LLM, conf=0.89)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The E-cadherin gene was efficiently deleted from the epidermis of K14-Cre/Ecad Fl/À mice, as no RNA expression was observed (Figure 1B).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Generation of mice lacking E-cadherin in the epidermis
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 40
- Probably not a substantial claim. 35
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“Both phenotypes are not observed in K14-Cre/Ecad Fl/À mice (Young et al, 2003;Tinkle et al, 2004;this paper).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Loss of E-cadherin does not result in loss or impairment of cell contact formation
What the sources say
- Partly supportedcites Young et al, 2003 sourceExperimental — accuracy not yet measured
The “Generation of conditional E-cadherin-deficient mice” section identifies the mutants as Krox20-Cre; E-cadherin ±/lox, not K14-Cre/Ecad Fl/−. The “Reduced proliferation in hair follicles” section reports no detected increase in epidermal proliferation in those mutants, but the paper does not establish the absence of both blistering and overgrowth in the K14-Cre genotype. (LLM, conf=0.76)
- Disputedcites Tinkle et al, 2004 sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says older E-cadherin-null skin showed hyperproliferation and thickening, directly contrary to the claim that overgrowth was not observed. It also describes preservation of epidermal integrity, but that does not rescue the claim that neither phenotype occurred. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“For example, the tight junctional marker ZO-1 binds directly to a-catenin and this is considered an intermediate step in the formation of tight junctions (Itoh et al, 1997).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Introduction
What the sources say
- Supportedcites Itoh et al, 1997 source
The Discussion (page not provided) reports direct binding between ZO-1 and α-catenin. It also proposes that this interaction occurs early in epithelial junction formation, before ZO-1 may move from adherens junctions to tight junctions during maturation. The claim’s “considered” wording preserves that proposed, rather than established, sequence. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Claudin-1 is not a specific marker for tight junctions in the epidermis but, as described previously (Furuse et al, 2002), is found at the membrane of all epidermal layers in control mice (Figure 8A).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Increased permeability of tight junctions in the absence of E-cadherin
What the sources say
- Supportedcites Furuse et al, 2002 source
In the Results section on occludin and claudins (Fig. 4A), the paper reports claudin-1 throughout the plasma membranes of wild-type epidermal keratinocytes from the basal through granular layers. It also notes that staining in the uppermost granular layer was fairly weak. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The association of E-cadherin with the actin cytoskeleton is mediated by a-catenin that is linked to the cadherin via b-catenin (Rimm et al, 1995).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Introduction
What the sources say
- Partly supportedcites Rimm et al, 1995 sourceExperimental — accuracy not yet measured
The Abstract (p. 8813) reports that α-catenin binds F-actin and that β-catenin can bind the α-catenin–actin complex. It proposes α-catenin as a tether at E-cadherin-mediated contacts, but does not establish the claimed β-catenin link to E-cadherin; it also presents the tethering mechanism as a model rather than a settled fact. (LLM, conf=0.85)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Interestingly, mice deficient for the tight junctional protein claudin-1 also show extensive water loss, appear red, shiny and wrinkled, and die within the same time frame as our mutant mice negative for E-cadherin in the epidermis (Furuse et al, 2002).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Increased permeability of tight junctions in the absence of E-cadherin
What the sources say
- Partly supportedcites Furuse et al, 2002 sourceExperimental — accuracy not yet measured
The Results sections on postnatal lethality and epidermal barrier impairment report that claudin-1–deficient mice developed wrinkled skin, had excessive transepidermal water loss, and died within one day of birth (page unavailable). The paper does not describe them as red or shiny. The comparison with the citing authors’ E-cadherin mutants depends on the citing authors’ own findings, not this source. (LLM, conf=0.87)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In vitro studies have shown that E-cadherin is not only necessary for adherens junction formation but its adhesive activity is also crucial for the assembly of other junctional complexes such as desmosomes, gap junctions and tight junctions (Gumbiner et al, 1988;Musil et al, 1990;Watabe et al, 1994).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Introduction
What the sources say
- Partly supportedcites Gumbiner et al, 1988 sourceExperimental — accuracy not yet measured
The paper identifies uvomorulin as E-cadherin, and its discussion concludes that formation of adherens junctions, desmosomes, and tight junctions similarly depends on uvomorulin function. It does not address gap-junction assembly, so that part of the claim is unsupported by this source. The supplied passages do not give a page number for the discussion. (LLM, conf=0.88)
- Partly supportedcites Musil et al, 1990 sourceExperimental — accuracy not yet measured
The Results (p. 2083) show that disrupting L-CAM-mediated cell adhesion inhibits a change associated with functional gap junctions; the paper also reports that introducing L-CAM corrected a gap-junction communication defect. This supports a role for cell adhesion in gap-junction formation or function, but the cited paper does not establish the claimed necessity for adherens-junction formation or for assembly of desmosomes and tight junctions. (LLM, conf=0.86)
- Partly supportedcites Watabe et al, 1994 sourceExperimental — accuracy not yet measured
The study reports that activating E-cadherin in PC9 cells produced adherens junctions, tight junctions and desmosomes (p. 247), and its Discussion calls cadherin-mediated contact a prerequisite for forming the latter two (pp. 252–253). But it does not show that E-cadherin's adhesive activity is crucial for gap-junction assembly: the Introduction (p. 247) only says that introducing a cadherin into cadherin-deficient cells enhances gap-junction formation. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Indeed, experiments in Drosophila have shown that mutations in junctional proteins not only affect junction formation but also disturb epithelial polarity, whereas polarity mutants have a profound effect on junction formation as well (Cox et al, 1996;Muller and Wieschaus, 1996;Tanentzapf et al, 2000).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Introduction
What the sources say
- Supportedcites Cox et al, 1996 source
The discussion (p. 145) reports that embryos lacking the junctional protein Armadillo cannot assemble adherens junctions and lose epithelial cell polarity. The paper also states, in its discussion of epithelial development, that the bazooka and stardust gene products are essential for initial adherens-junction assembly, supporting the sentence’s point about polarity mutants. (LLM, conf=0.90)
- Supportedcites Muller and Wieschaus, 1996 source
The Abstract (p. 149) reports that stardust–bazooka mutants fail to form a zonula adherens and lose the organized epithelial cell layer. The Results (p. 158) report disrupted junction formation in embryos with reduced Armadillo, a junctional protein; the paper also describes their loss of the orderly monolayer. Together, these findings support both directions of the cited claim in Drosophila embryos. (LLM, conf=0.93)
- Supportedcites Tanentzapf et al, 2000 source
In Results (Role of the Cadherin–Catenin Complex in the Differentiation of the FE; page unavailable), the paper reports that disrupting adherens junctions in arm mutant follicle cells compromises both lateral and apical membrane domains. In Discussion (Activity of Apical, Lateral, and Basal Cues; page unavailable), it also reports prior findings that the apical polarity factor Crb is needed for zonula adherens formation in Drosophila embryos. Together, these support the two directions of the cited claim. (LLM, conf=0.89)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“E-cadherin is important for tissue morphogenesis and polarity (Larue et al, 1994).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Introduction
What the sources say
- Supportedcites Larue et al, 1994 source
The Results and Discussion (page not provided) state that E-cadherin is central to early morphogenetic events and that its abundance is crucial for cell polarity and trophectoderm epithelial integrity. This supports the citing sentence’s broad paraphrase. (LLM, conf=0.93)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, such a model does not explain why specifically claudin-1, but not claudin-4 or occludin, is lacking from the granular layer whereas ZO-1 interacts with the C-terminus of all claudins and occludin (Fanning et al, 1998;Itoh et al, 1999).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Does aPKC play a role in E-cadherin-mediated epidermal tight junction formation?
What the sources say
- Partly supportedcites Fanning et al, 1998 sourceExperimental — accuracy not yet measured
The Results (page not provided) report that ZO-1 binds a fusion protein containing the C-terminal region of occludin. The paper does not report interactions with claudins, so it does not support the claim about all claudins. (LLM, conf=0.90)
- Partly supportedcites Itoh et al, 1999 sourceExperimental — accuracy not yet measured
The Results (page unavailable) show that ZO-1 binds the C-terminal regions of claudin-1 through claudin-8, which includes claudin-1 and claudin-4. The paper also reports binding between ZO-1 and the C-terminal tail of occludin. But it describes at least 16 claudin family members and does not establish binding to all of them. (LLM, conf=0.89)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In addition, Rac activity has been implicated in the regulation of tight junction gate and fence function (Jou et al, 1998).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > The small GTPase Rac may mediate E-cadherindependent localization of activated aPKC
What the sources say
- Supportedcites Jou et al, 1998 source
The Abstract states that Rac1 mutants perturbed tight junction gate function and disrupted fence function in MDCK cells. The Discussion section ‘TJ Gate and Fence Functions are Disrupted by RhoA and Rac1 Mutants’ likewise reports effects on both functions, supporting the citing sentence’s hedged claim. (LLM, conf=0.95)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Nevertheless, these authors did observe a slight disturbance in the epidermal barrier but have not examined tight junctional markers and function.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Epidermal E-cadherin is essential for water barrier formation
What the sources say
- Partly supportedcites Tinkle et al, 2004 sourceExperimental — accuracy not yet measured
The Results report reduced filaggrin and loricrin in E-cadherin-null epidermis and say these changes were suggestive of a barrier defect that was likely mild. The paper does not report a direct barrier-function measurement, so “observed” overstates that inference. Its reported junctional analyses concern adherens junctions and desmosomes, not tight-junction markers or function. (LLM, conf=0.85)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The discovery of tight junctions and their importance in the epidermal water barrier therefore came as a surprise (Brandner et al, 2002;Furuse et al, 2002).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > E-cadherin contributes to epidermal barrier formation by regulating the incorporation of claudins into tight junctions
What the sources say
- Not checked — no full text of the sourcecites Brandner et al, 2002 source
- Supportedcites Furuse et al, 2002 source
The Abstract says tight junctions had not been thought important to the mammalian epidermal barrier and calls the findings unexpected. It reports that claudin-1–deficient mice had severe transepidermal water loss and that continuous tight junctions were identified in the epidermis. The Discussion likewise contrasts this finding with the previously accepted emphasis on the cornified envelope and lipid lamellae. Page numbers are not provided in our copy. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Every source the paper cites for this claim was checked and supports it.
In the paper
“This layer consists of dead keratin-filled cells embedded in a lipid matrix, thus providing a tough insoluble layer that separates the outside from the inside (Nemes and Steinert, 1999).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > E-cadherin contributes to epidermal barrier formation by regulating the incorporation of claudins into tight junctions
What the sources say
- Supportedcites Nemes and Steinert, 1999 source
The Introduction describes the cornified layer as keratin-rich corneocytes held together by intercorneocyte lipids and calls each cell’s envelope sturdy and extremely insoluble. The Abstract identifies these dead stratum corneum cells and their surrounding lipids as a barrier between the body and the environment. (LLM, conf=0.91)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Inactivation of a-catenin in the epidermis resulted in severe blistering and overgrowth (Vasioukhin et al, 2001).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Loss of E-cadherin does not result in loss or impairment of cell contact formation
What the sources say
- Partly supportedcites Vasioukhin et al, 2001 sourceExperimental — accuracy not yet measured
The discussion reports uncontrolled growth and large epidermal masses after α-catenin ablation, supporting the overgrowth claim. Figure 2 reports impaired intercellular junctions in the knockout epidermis, but the passages found do not report severe blistering; that part is unsupported. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Alternatively, growth regulation may be a cadherin-independent function of a-catenin (Vasioukhin et al, 2001).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Loss of E-cadherin does not result in loss or impairment of cell contact formation
What the sources say
- Partly supportedcites Vasioukhin et al, 2001 sourceExperimental — accuracy not yet measured
The Discussion (page unavailable in our copy) says α-catenin’s effects on hyperproliferation can be separated from its effects on cell–cell adhesion, supporting a possible growth-regulatory role beyond adhesion. But the paper also links the altered growth signaling to an E-cadherin/β-catenin complex with IRS-1; it does not establish that growth regulation is independent of cadherin itself. (LLM, conf=0.83)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In vitro studies using mostly simple epithelial cells have indicated that E-cadherin-mediated adhesion is a necessary prerequisite for the formation of other cell junctions, such as desmosomes, gap junctions and tight junctions (Gumbiner et al, 1988;Musil et al, 1990;Watabe et al, 1994).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > E-cadherin is specifically required for correct tight junction formation
What the sources say
- Partly supportedcites Gumbiner et al, 1988 sourceExperimental — accuracy not yet measured
The Abstract (p. 1575) reports that blocking uvomorulin, also identified as E-cadherin, similarly inhibited formation of desmosomes and tight junctions in cultured MDCK epithelial cells. It does not report testing gap junction formation, so that part of the citing sentence is not supported by this paper. (LLM, conf=0.88)
- Partly supportedcites Musil et al, 1990 sourceExperimental — accuracy not yet measured
The Results (p. 2083) show that introducing L-CAM into S180 cells increased gap-junction formation and communication, while disrupting L-CAM-mediated adhesion inhibited connexin43 processing. The Discussion says strong cell association *may* be important for gap-junction formation. The paper does not establish E-cadherin-mediated adhesion as a necessary prerequisite, or address desmosome and tight-junction formation as the claim states. (LLM, conf=0.87)
- Partly supportedcites Watabe et al, 1994 sourceExperimental — accuracy not yet measured
The Introduction (pp. 247–248) describes cadherins as prerequisites for epithelial junctional complexes, and the Discussion (p. 252) presents evidence that E-cadherin-mediated contact precedes tight-junction and desmosome formation. For gap junctions, however, the paper says cadherin introduction enhances their formation; it does not establish E-cadherin-mediated adhesion as necessary for them. (LLM, conf=0.84)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Indeed, staining for E-cadherin was negative in the newborn epidermis of mutant mice, whereas E-cadherin staining was found as expected in all layers of the epidermis in the skin of newborn control mice (Figure 1C).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Generation of mice lacking E-cadherin in the epidermis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although its localization is still confined to the granular layer in K14-Cre/Ecad Fl/À mice, its distribution on the membrane is altered, showing a more punctate staining pattern.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Increased permeability of tight junctions in the absence of E-cadherin
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The mutant skin appears more red and shiny than that of their control littermates, and has a parchmentlike resemblance.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Early deletion of E-cadherin in the epidermis results in perinatal death due to water loss
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Indeed, partial penetration of toluidine blue is observed around the paws and the ventral side in control E16.5 embryos and this pattern is similar for K14-Cre/Ecad Fl/À E16.5 embryos (Figure 6B).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > The outside-in barrier is functional in K14-Cre/Ecad Fl/À mice
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This resulted in either K14-Cre/Ecad Fl/Fl or K14-Cre/Ecad Fl/À mice (Figure 1A) that both died within 1 day after birth.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Generation of mice lacking E-cadherin in the epidermis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Differentiation markers and proliferation appeared normal (Supplementary Figure 2).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Cell-cell contacts are maintained in the absence of E-cadherin
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“P-cadherin expression is upregulated (Figure 2B) but was still mainly found in the basal layer of the epidermis of E-cadherin mutant mice (Figure 2A), suggesting that P-cadherin only compensates for the loss of Ecadherin in the basal layer.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Cell-cell contacts are maintained in the absence of E-cadherin
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Absence of E-cadherin leads to improper localization of key tight junctional proteins, resulting in permeable tight junctions and thus altered epidermal resistance.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Par3 is found at cell-cell contacts in all suprabasal layers of the epidermis, and its distribution (Figure 9A) and amount of protein (Figure 9B) were not significantly altered in K14-Cre/Ecad Fl/À mice.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Increased permeability of tight junctions in the absence of E-cadherin
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“This fits with the observation that our mice lack whiskers despite the presence of hair follicles (not shown).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Epidermal E-cadherin is essential for water barrier formation
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, E-cadherin loss did not alter the distribution of Par3, which is still found at sites of cell-cell contacts in the epidermis.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Does aPKC play a role in E-cadherin-mediated epidermal tight junction formation?
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although loss of E-cadherin does not result in absence of ZO-1 from the membrane, its distribution is dramatically altered, suggesting that it is no longer incorporated into tight junctions.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Does aPKC play a role in E-cadherin-mediated epidermal tight junction formation?
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Normal structure and cell-cell contacts in K14-Cre/Ecad Fl/À mice.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Rac activation assays
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, such a model does not explain why specifically claudin-1, but not claudin-4 or occludin, is lacking from the granular layer whereas ZO-1 interacts with the C-terminus of all claudins and occludin (Fanning et al, 1998;Itoh et al, 1999).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Does aPKC play a role in E-cadherin-mediated epidermal tight junction formation?
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Desmosomes are abundantly present in the absence of E-cadherin, and desmosomal markers appear to have their normal differentiation pattern within the epidermis.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > E-cadherin is specifically required for correct tight junction formation
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, this is perhaps unlikely in the upper layers of the epidermis, since Cdc42 expression appears to be confined to the basal layer and is not altered by the loss of E-cadherin.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > The small GTPase Rac may mediate E-cadherindependent localization of activated aPKC
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our results clearly show that loss of E-cadherin in the epidermis alters the permeability of tight junctions (Figure 7A) resulting in decreased epithelial resistance (Figure 7B).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > E-cadherin contributes to epidermal barrier formation by regulating the incorporation of claudins into tight junctions
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The activity of the Par3/Par6/aPKC polarity protein complex has been implicated in the formation of tight junctions in simple epithelia (Macara, 2004).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Introduction
What the sources say
- Not checked — no full text of the sourcecites Macara, 2004 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Its activation depends on the formation of cell-cell contacts (Yamanaka et al, 2001) and Armadillo, the fly b-catenin homologue, is important for proper localization of this complex in Drosophila (Bilder et al, 2003;Tanentzapf and Tepass, 2003).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Introduction
What the sources say
- Not checked — no full text of the sourcecites Yamanaka et al, 2001 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“The size and ion selectivity of tight junctions is variable within different tissues and depends on the type and levels of expression of claudins, four span transmembrane molecules, which constitute the tight junctional paired strands (Inai et al, 1999;Colegio et al, 2003).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Surprisingly, our results indicate that E-cadherin is specifically required for tight junction, but not desmosome, formation and this appears to involve signalling rather than cell contact formation.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Abstract
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Another catenin, p120 ctn , also binds directly to the cadherin and regulates the stability of the cadherin complex at the cell surface (Reynolds and Roczniak-Ferguson, 2004).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Introduction
What the sources say
- Not checked — no full text of the sourcecites Reynolds and Roczniak-Ferguson, 2004 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Upon establishing cell-cell adhesion, cadherins cluster in specialized cell junctions, known as adherens junctions, which associate with the actin cytoskeleton (Gottardi et al, 2002).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Introduction
What the sources say
- Not matchedcites Gottardi et al, 2002
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, our results show that even though tight junction formation is not completely disturbed, key components are not properly incorporated, which likely underlies the functional impairment of tight junctions.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Increased permeability of tight junctions in the absence of E-cadherin
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Activation of the Par3/Par6/aPKC complex is achieved by binding to the small GTPase Cdc42, resulting in the phosphorylation and activation of aPKC (Joberty et al, 2000;Lin et al, 2000).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“One of these polarity complexes consists of the Par3/ Par6/atypicalPKC (aPKC) complex, which localizes to the apical junctional complex in Drosophila and to tight junctions in mammalian epithelial cells (Nelson, 2003).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Introduction
What the sources say
- Not checked — no full text of the sourcecites Nelson, 2003 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“This junctional complex assembly coincides with the establishment of cell polarity and enrichment at the cell junctions of several protein complexes known to be essential for polarity, suggesting an intimate relationship between junction formation and polarity (Nelson, 2003).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Introduction
What the sources say
- Not checked — no full text of the sourcecites Nelson, 2003 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Two classical cadherins are expressed within the epidermis: P-cadherin, which is confined to the basal layer, and E-cadherin found in all epidermal cell layers (Jensen et al, 1997).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Introduction
What the sources say
- Not checked — no full text of the sourcecites Jensen et al, 1997 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Its activation depends on the formation of cell-cell contacts (Yamanaka et al, 2001) and Armadillo, the fly b-catenin homologue, is important for proper localization of this complex in Drosophila (Bilder et al, 2003;Tanentzapf and Tepass, 2003).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Tight junctions act as selective permeability barriers but also form a fence that physically separates the apical membrane domain from the basolateral domain in simple epithelial cells (Anderson et al, 2004).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Introduction
What the sources say
- Not checked — no full text of the sourcecites Anderson et al, 2004 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Desmosomes provide tissues with stable and strong cell-cell adhesion (Getsios et al, 2004).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Introduction
What the sources say
- Not checked — no full text of the sourcecites Getsios et al, 2004 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This suggested that tight junctions are either absent or are no longer properly functioning in E-cadherin mutant skin.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Increased permeability of tight junctions in the absence of E-cadherin
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We therefore conclude that maturation of the cornified layer developed normal in the absence of E-cadherin, resulting in a properly functioning outside-in barrier.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > The outside-in barrier is functional in K14-Cre/Ecad Fl/À mice
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In addition, claudin-6 overexpression in the skin also disturbs barrier function (Turksen and Troy, 2002).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Introduction
What the sources say
- Not checked — no full text of the sourcecites Turksen and Troy, 2002 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Experiments were repeated three times.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Rac activation assays
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, no differences in the levels of activated Rac were found between skin lysates of control and K14-Cre/ Ecad Fl/À mice (Figure 9C), suggesting that E-cadherin is important for the recruitment of activated Rac to sites of cell-cell contact but not for its activation per se.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Increased permeability of tight junctions in the absence of E-cadherin
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Surprisingly, this effect is not due to a loss of cell contact formation or altered epidermal differentiation.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Epidermal E-cadherin is essential for water barrier formation
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“It has been shown that Rac can bind to Par6 and thus potentially activate aPKC (Johansson et al, 2000;Lin et al, 2000).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > The small GTPase Rac may mediate E-cadherindependent localization of activated aPKC
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, an important implication of our work is that this effect of E-cadherin on tight junction formation is not simply the result of cell adhesion but rather seems to arise from signalling, most likely by recruitment of the small GTPase Rac and atypical PKC to sites of cell-cell contact.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > E-cadherin is specifically required for correct tight junction formation
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The increased expression of these two adhesive systems may explain why no blistering occurs and why cell contact formation appears normal in newborn epidermis (Figure 4).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Loss of E-cadherin does not result in loss or impairment of cell contact formation
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In our K14-cre/Ecad Fl/À mice, E-cadherin is already almost completely absent at E15.5 (Figure 1C) shortly before the onset of barrier formation (Hardman et al, 1998), perhaps explaining why loss of E-cadherin has more dramatic consequences in our mice.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Epidermal E-cadherin is essential for water barrier formation
What the sources say
- Not checked — no full text of the sourcecites Hardman et al, 1998 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, P-cadherin is only substantially upregulated in the basal layer in the absence of E-cadherin and it may require cadherin expression in the suprabasal layers to support tight junctions.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > E-cadherin is specifically required for correct tight junction formation
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Most data point to a role for Cdc42 as the small GTPase that activates the aPKC/Par3/Par6 complex (Macara, 2004).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > The small GTPase Rac may mediate E-cadherindependent localization of activated aPKC
What the sources say
- Not checked — no full text of the sourcecites Macara, 2004 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We were unable to detect any obvious functional differences in the barrier function of the stratum corneum between control and K14-Cre/Ecad Fl/À mice, indicating that the cornified layer is not disturbed and still constitutes a functional barrier.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > E-cadherin contributes to epidermal barrier formation by regulating the incorporation of claudins into tight junctions
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, E-cadherin is essential for activation of aPKC at the appropriate localization or for recruitment of activated forms to sites of cell-cell contact.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Increased permeability of tight junctions in the absence of E-cadherin
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The upregulation of P-cadherin may also be sufficient to confer normal growth and differentiation properties to the basal epidermal keratinocytes in the absence of E-cadherin.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Loss of E-cadherin does not result in loss or impairment of cell contact formation
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Instead, we find that essential tight junctional components are not properly targeted to tight junctions, resulting in malfunctioning of these structures.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > Epidermal E-cadherin is essential for water barrier formation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The ability to initiate and maintain cell-cell contacts is considered key to this E-cadherin function (Nelson, 2003).”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > E-cadherin is specifically required for correct tight junction formation
What the sources say
- Not checked — no full text of the sourcecites Nelson, 2003 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We propose that Rac may mediate E-cadherin-induced recruitment or activation of aPKC at cell-cell contacts in the epidermis.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > The small GTPase Rac may mediate E-cadherindependent localization of activated aPKC
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Claudins determine size and ion specificity of tight junctional barriers.”
§ E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions > E-cadherin contributes to epidermal barrier formation by regulating the incorporation of claudins into tight junctions
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Moreover, the TJ markers ZO-1 and occludin lost their continuous and linear apical distribution in Ecadepi−/− SG2. Instead, these proteins showed a more punctate pattern at cellular interfaces, revealing many breaks (Fig. 3d), thus explaining why in vivo TJ barrier function is disturbed upon loss of E-cadherin10.”
From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [10]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Interestingly, this punctate intercellular contact pattern of ZO-1 and occludin was also observed in Ecadepi−/− spinous layers, indicating premature formation of non-functional TJ-like structures (Fig. 3d, f; Supplementary Fig. 3e; ref. 10).”
From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [10]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“A functional SC barrier is first formed in dorsal epidermis at embryonic day (E)16.5, spreading only to the ventral side one day later10, 20.”
From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [10]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Interestingly, this increased activity was not associated with enhanced proliferation in vitro or in vivo (ref. 10; Supplementary Fig. 7g).”
From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [10]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In contrast, loss of vinculin in the epidermis did not affect either apical ZO-1 positioning or F-actin distribution in SG2 and did not result in major barrier defects in vivo, as vinculinepi−/− mice are viable, unlike Ecadepi−/− mice generated using the same K14-Cre line10.”
From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [10]
Experimental — accuracy not yet measured
The cited source says what the claim attributes to it.
In the citing paper
“In the epidermis loss of E-cadherin expressed in all viable layers interferes with the TJ barrier, resulting in perinatal death10.”
From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing paper
“This was surprising as desmosomes, considered an important mechanical unit, are formed in these cells10, 23.”
From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing paper
“In vivo, loss of epidermal vinculin did not result in perinatal lethality unlike loss of E-cadherin10.”
From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [10]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“In conclusion, E-cadherin controls the polarized localization and activity status of suprabasal EGFR, which is uncoupled from growth10.”
From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [10]
Experimental — accuracy not yet measured
Citations
Cites
Claudin-based tight junctions are crucial for the mammalian epidermal barrier
Furuse, M., Hata, M., Furuse, K., Yoshida, Y., Haratake, A., Sugitani, Y., Noda, T., Kubo, A., & Tsukita, S. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200110122 · Cited by 1,512
Fanning, A. S., Jameson, B. J., Jesaitis, L. A., & Anderson, J. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.45.29745 · Cited by 1,432
Itoh, M., Furuse, M., Morita, K., Kubota, K., Saitou, M., & Tsukita, S. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.147.6.1351 · Cited by 1,151
E-cadherin null mutant embryos fail to form a trophectoderm epithelium.
Larue, L., Ohsugi, M., Hirchenhain, J., & Kemler, R. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.17.8263 · Cited by 930
Self-citationThe cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42
Joberty, G., Petersen, C., Gao, L., & Macara, I. G. (2000) · Nature Cell Biology · doi:10.1038/35019573 · Cited by 928
Gumbiner, B., Stevenson, B., & Grimaldi, A. (1988) · The Journal of cell biology · doi:10.1083/jcb.107.4.1575 · Cited by 799
A mammalian PAR-3–PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity
Lin, D., Edwards, A. S., Fawcett, J. P., Mbamalu, G., Scott, J. D., & Pawson, T. (2000) · Nature Cell Biology · doi:10.1038/35019582 · Cited by 743
Rimm, D. L., Koslov, E. R., Kebriaei, P., Cianci, C. D., & Morrow, J. S. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.19.8813 · Cited by 735
Pérez‐Moreno, M., Jamora, C., & Fuchs, E. V. (2003) · Cell · doi:10.1016/s0092-8674(03)00108-9 · Cited by 717
Adaptation of core mechanisms to generate cell polarity
Nelson, W. J. (2003) · Nature · doi:10.1038/nature01602 · Cited by 716
Research works printed but not linked: 1
- Gottardi CJ, Niessen CM, Gumbiner BM (2002) The adherens junction. In Cell Adhesion, The Frontiers in Molecular Biology Series, Hames BD, Glover DM, Beckerle M (eds). chap 8, Oxford University Press
Cited by
Sorted by citations
The skin: an indispensable barrier
Proksch, E., Brandner, J. M., & Jensen, J. (2008) · Experimental Dermatology · doi:10.1111/j.1600-0625.2008.00786.x · Cited by 2,054
The cell-cell adhesion molecule E-cadherin
Roy, F. M. V., & Berx, G. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8281-1 · Cited by 1,392
Cadherins and cancer: how does cadherin dysfunction promote tumor progression?
Jeanes, A., Gottardi, C. J., & Yap, A. S. (2008) · Oncogene · doi:10.1038/onc.2008.343 · Cited by 791
“Whereas acutely perturbing E-cadherin can prevent cells from effectively establishing a polarized phenotype, steady-state depletion of E-cadherin often does not overtly affect maintenance of polarity (Tunggal et al., 2005; Capaldo and Macara, 2007).”
E-cadherin, β-catenin, and ZEB1 in malignant progression of cancer
Schmalhofer, O., Brabletz, S., & Brabletz, T. (2009) · Cancer and Metastasis Reviews · doi:10.1007/s10555-008-9179-y · Cited by 771
“basal cell polarity and formation of tight junctions [36].”
BackgroundTight junctions/adherens junctions: basic structure and function
Niessen, C. M. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700865 · Cited by 756
“This was associated with inappropriate localization of polarity proteins like aPKC, which is localized not only at tight junctions but at cell–cell contacts in all viable epidermal layers (Tunggal et al ., 2005).”
BackgroundSelf-citationInvolvement of Members of the Cadherin Superfamily in CancerPreprint
Berx, G., & Roy, F. M. V. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a003129 · Cited by 706
“In contrast, in mouse models specific loss of E-cadherin in the skin and the mammary gland is not sufficient for tumorigenesis (Boussadia et al. 2002; Tinkle et al. 2004; Tunggal et al. 2005).”
BackgroundDerksen, P. W. B., Liu, X., Saridin, F., van der Gulden, H., Zevenhoven, J., Evers, B., van Beijnum, J. R., Griffioen, A. W., Vink, J., Krimpenfort, P., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.09.013 · Cited by 591
“These findings are consistent with previous work showing that conditional inactivation of E-cadherin in either skin or mammary epithelium does not induce tumor formation (Boussadia et al., 2002; Young et al., 2003; Tinkle et al., 2004; Tunggal et al., 2005).”
ResultDeconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis
Simpson, C. L., Patel, D. M., & Green, K. J. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3175 · Cited by 516
“Epidermal adherens junctions are composed of the classic cadherins — E-cadherin and placental cadherin (P-cadherin; also known as cadherin 3) — both of which are important for skin morphogenesis: targeted ablation of E-cadherin causes hyperproliferation, defective differentiation and impaired barrier formation with lo…”
BackgroundEpidermal barrier formation and recovery in skin disorders
Segre, J. A. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28521 · Cited by 519
Cell–Cell Junctions Organize Structural and Signaling NetworksPreprint
García, M. Á., Nelson, W. J., & Chavez, N. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a029181 · Cited by 540
“…in the epidermis of mice resulted in thickening of the epidermis and defects in terminal differen-tiationaswellasperinataldeathduetoimproper tight junction formation (Tinkle et al. 2004; Tunggal et al. 2005); hyperplasia also developed in aging keratinocytes derived from E-cadherin-knockout mice.”
BackgroundNiessen, C. M., Leckband, D., & Yap, A. S. (2011) · Physiological Reviews · doi:10.1152/physrev.00004.2010 · Cited by 427
“Thus conditional disruption of E-cadherin in the mouse skin was associated with mild adhesion defects (370, 423) or defective tight junctions (379), but did not disrupt epidermal integrity.”
BackgroundSelf-citationVandenesch, F., Lina, G., & Henry, T. (2012) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2012.00012 · Cited by 405
Aghapour, M., Raee, P., Moghaddam, S. J., Hiemstra, P. S., & Heijink, I. H. (2017) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2017-0200tr · Cited by 399
“In line with this, inhibition of PKD3 at baseline has been shown to enhance electrical resistance of airway epithelial cells in vitro, possibly via upregulation of CLDN1 (153).”
Deli, M. A. (2008) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2008.09.016 · Cited by 385
“Loss of E-cadherin in the epidermis, by conditionally inactivating its gene in mice, results in perinatal death due to the inability to retain a functional epidermal water barrier [47].”
BackgroundEpithelial cell dysfunction, a major driver of asthma development
Heijink, I. H., Kuchibhotla, V. N. S., Roffel, M. P., Maes, T., Knight, D. A., Sayers, I., & Nawijn, M. C. (2020) · Allergy · doi:10.1111/all.14421 · Cited by 349
Mechanisms Regulating Epithelial Stratification
Koster, M. I., & Roop, D. R. (2007) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.23.090506.123357 · Cited by 324
Calcium regulation of keratinocyte differentiation
Bikle, D. D., Xie, Z., & Tu, C. (2012) · Expert Review of Endocrinology & Metabolism · doi:10.1586/eem.12.34 · Cited by 345
Jantsch, J., Schatz, V., Friedrich, D., Schröder, A., Kopp, C., Siegert, I., Maronna, A., Wendelborn, D., Linz, P. R., Binger, K. J., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.02.003 · Cited by 318
“The skin epidermis harbors a liquid-liquid interphase,where tight- junctions compartmentalize the extracellular fluid space and pre- vent transepidermal water losses (Furuse et al., 2002; Tunggal et al., 2005).”
BackgroundSherrill, J. D., KC, K., Wu, D. X.-Y., Djukic, Z., Caldwell, J. M., Stucke, E. M., Kemme, K. A., Costello, M. S., Mingler, M. K., Blanchard, C., et al. (2013) · Mucosal Immunology · doi:10.1038/mi.2013.90 · Cited by 314
Miroshnikova, Y. A., Le, H. Q., Schneider, D., Thalheim, T., Rübsam, M., Bremicker, N., Polleux, J., Kamprad, N., Tarantola, M., Wang, I., et al. (2017) · Nature Cell Biology · doi:10.1038/s41556-017-0005-z · Cited by 304
Self-citationIntercellular Junction Assembly, Dynamics, and HomeostasisPreprint
Green, K. J., Getsios, S., Troyanovsky, S. M., & Godsel, L. M. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a000125 · Cited by 259
“Although depletion of classical cadherins interferes with epidermal cohesion and the tight junction barrier in vivo, desmosomes still form in epidermis lacking classical cadherins or alpha-catenin (Vasioukhin et al. 2001a; Tunggal et al. 2005; Tinkle et al. 2008).”
BackgroundCapaldo, C., & Macara, I. G. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-05-0471 · Cited by 258
“Postnatal lethality in mice with a conditional E-cadherin knockout in skin is due to failure of the epidermis to prevent water loss (Tinkle et al., 2004; Tunggal et al., 2005).”
BackgroundInfluentialMechanisms of cancer metastasis
Castañeda, M., den Hollander, P., Kuburich, N. A., Rosen, J. M., & Mani, S. A. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.10.006 · Cited by 279
The role of tight junctions in skin barrier function and dermal absorption
Bäsler, K., Bergmann, S., Heisig, M., Nägel, A., Zorn‐Kruppa, M., & Brandner, J. M. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.08.007 · Cited by 255
Cadherin-based intercellular adhesions organize epithelial cell–matrix traction forces
Mertz, A. F., Che, Y., Banerjee, S., Goldstein, J. M., Rosowski, K. A., Revilla, S. F., Niessen, C. M., Marchetti, M. C., Dufresne, E. R., & Horsley, V. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1217279110 · Cited by 243
“We further investigated the role of classical cadherins using primary keratinocytes from an epidermal-E-cadherin–knockout (KO) mouse (46).”
BackgroundSelf-citationBreitkreutz, D., Koxholt, I., Thiemann, K., & Nischt, R. (2013) · BioMed Research International · doi:10.1155/2013/179784 · Cited by 267
Mertens, A. E. E., Rygiel, T. P., Olivo, C., van der Kammen, R., & Collard, J. G. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200502129 · Cited by 238
“These conclusions are consistent with studies that show the activity of Cdc42 is dispensable for cell polarization in epithelial MDCK cells and epidermal keratinocytes (Gao et al., 2002; Tunggal et al., 2005), although another study has implicated Cdc42 in TJ biogenesis (Fukuhara et al., 2003).”
ResultBattle, M. A., Konopka, G., Parviz, F., Gaggl, A. L., Yang, C., Sladek, F. M., & Duncan, S. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600246103 · Cited by 246
Airway epithelial regulation of pulmonary immune homeostasis and inflammation
Hallstrand, T. S., Hackett, T., Altemeier, W. A., Matute‐Bello, G., Hansbro, P. M., & Knight, D. A. (2013) · Clinical Immunology · doi:10.1016/j.clim.2013.12.003 · Cited by 233
“E-cadherin provides the architectural support required to form other junctional complexes, as delocalization of the TJ proteins ZO-1, occludin and claudins occurs following distorted AJ architecture [1,2].”
BackgroundEpidermal tight junctions in health and disease
Brandner, J., Zorn‐Kruppa, M., Yoshida, T., Moll, I., Beck, L. A., & Benedetto, A. D. (2014) · Tissue Barriers · doi:10.4161/21688370.2014.974451 · Cited by 227
“When applying this tracer to the dermis its movement out is limited by TJs, while it is largely restricted by the SC when applied on the skin surface.(3,11,15,16,21,29,37) This suggests that epidermal barrier function is quite complex, and the relative importance of the 2 major barrier structures (SC and TJ) may be in…”
BackgroundE-cadherin: gatekeeper of airway mucosa and allergic sensitization
Nawijn, M. C., Hackett, T., Postma, D. S., van Oosterhout, A. J. M., & Heijink, I. H. (2011) · Trends in Immunology · doi:10.1016/j.it.2011.03.004 · Cited by 222
Cadherins in development and cancer
Stemmler, M. P. (2008) · Molecular BioSystems · doi:10.1039/b719215k · Cited by 219
Tay, C. Y., Setyawati, M. I., Xie, J., Parak, W. J., & Leong, D. T. (2014) · Advanced Functional Materials · doi:10.1002/adfm.201401664 · Cited by 215
Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease
Kovalenko, A., Kim, J., Kang, T., Rajput, A., Bogdanov, K., Dittrich‐Breiholz, O., Kracht, M., Brenner, O. J., & Wallach, D. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090616 · Cited by 214
“JEM VOL. 206, September 28, 2009 ARTICLE 2165 function in vivo (Tunggal et al., 2005).”
BackgroundLoss of E-Cadherin-Dependent Cell–Cell Adhesion and the Development and Progression of CancerPreprint
Bruner, H. C., & Derksen, P. W. B. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a029330 · Cited by 222
“This is of interest because E-cadherin inactivation in postnatal skin is tolerated because of Pcadherin redundancy (Tinkle et al. 2004; Tunggal et al. 2005), implying a tissue-specific and context-dependent role for E-cadherin in the mammary gland.”
BackgroundRübsam, M., Mertz, A. F., Kubo, A., Marg, S., Jüngst, C., Goranci-Buzhala, G., Schauss, A. C., Horsley, V., Dufresne, E. R., Moser, M., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01170-7 · Cited by 210
Self-citationA Key Role for E-cadherin in Intestinal Homeostasis and Paneth Cell Maturation
Schneider, M. R., Dahlhoff, M., Horst, D. A., Hirschi, B., Trülzsch, K., Müller‐Höcker, J., Vogelmann, R., Allgäuer, M., Gerhard, M., Steininger, S., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0014325 · Cited by 206
“Here, loss of E-cadherin resulted in death of mice shortly after birth due to dehydration [41], altered differentiation [39], and disturbed epidermal integrity [40].”
BackgroundCoherent angular motion in the establishment of multicellular architecture of glandular tissues
Tanner, K., Mori, H., Mroue, R. M., Bruni‐Cardoso, A., & Bissell, M. J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1119578109 · Cited by 198
The TRPV4 Channel Contributes to Intercellular Junction Formation in Keratinocytes
Sokabe, T., Fukumi-Tominaga, T., Yonemura, S., Mizuno, A., & Tominaga, M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.103606 · Cited by 198
12R-lipoxygenase deficiency disrupts epidermal barrier function
Epp, N., Fürstenberger, G., Müller, K., de Juanes, S., Leitges, M., Haußer, I., Thieme, F., Liebisch, G., Schmitz, G., & Krieg, P. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200612116 · Cited by 194
“…mouse models with epidermal barrier defects, including mice defi cient in KLF4 (Segre et al., 1999), claudin (Furuse et al., 2002), E-cadherin (Tunggal et al., 2005), LEKTI (Descargues et al., 2005), CAP1 (Leyvraz et al., 2005), and FATP4 (Herrmann et al., 2003), exhibited substantially less…”
BackgroundMethodInfluentialden Bossche, J. V., MALISSEN, B., Mantovani, A., BAETSELIER, P. D., & Ginderachter, J. A. V. (2011) · Blood · doi:10.1182/blood-2011-10-384289 · Cited by 185
“40-42 Next, PtdIns(3,4,5)P3 production in these nascent Ecadherin contacts triggers the recruitment of proteins containing pleckstrin homology domains, including Akt.”
BackgroundGladden, A. B., Hebert, A. M., Schneeberger, E. E., & McClatchey, A. I. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.10.008 · Cited by 172
“Indeed, the polarity proteins Par3 and aPKC localize to the apical junction and are necessary both for the establishment of polarity and the formation of TJs (Goldstein and Macara, 2007; Helfrich et al., 2007; Suzuki et al., 2002; Suzuki and Ohno, 2006).”
BackgroundInfluentialKuo, I., Carpenter-Mendini, A. B., Yoshida, T., McGirt, L. Y., Ivanov, A. I., Barnes, K. C., Gallo, R. L., Borkowski, A. W., Yamasaki, K., Leung, D. Y. M., et al. (2012) · Journal of Investigative Dermatology · doi:10.1038/jid.2012.437 · Cited by 177
“…TJ components in cultured keratinocytes (Amagai et al., 2000; Baltes et al., 2004; Djalilian et al., 2006; Furuse et al., 2001; Furuse et al., 2002; Gareus et al., 2007; Kretz et al., 2004; Lucke et al., 1999; Ma et al., 2004; Ohnemus et al., 2008; Tunggal et al., 2005; Yuki et al., 2011a).”
BackgroundAdhesive and Signaling Functions of Cadherins and Catenins in Vertebrate DevelopmentPreprint
Stępniak-Konieczna, E., Radice, G. L., & Vasioukhin, V. I. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a002949 · Cited by 175
“Intriguingly, however, deletion of E-cadherin in embryonic skin epidermis did not result in a significant impairment of AJs, most likely because of compensatory up-regulation of P-cadherin (Young et al. 2003; Tinkle et al. 2004; Tunggal et al. 2005).”
BackgroundJensen, J., Pfeiffer, S., Witt, M., Bräutigam, M., Neumann, C., Weichenthal, M., Schwarz, T., Fölster‐Holst, R., & Proksch, E. (2009) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.07.015 · Cited by 166
Müller, E. J., Williamson, L., Kolly, C., & Suter, M. M. (2008) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5701248 · Cited by 166
“In support of a possible involvement of E-cadherin in growth control in keratinocytes in vivo, E-cadherinknockout epidermis displays some hyperproliferation, which however appears to be limited due to compensatory upregulation of P-cadherin (Young et al., 2003; Tinkle et al., 2004; Tunggal et al., 2005) or (as will be…”
BackgroundFunctions of EpCAM in physiological processes and diseases (Review)
Huang, L., Yang, Y., Yang, F., Liu, S., Zhu, Z., Lei, Z., & Guo, J. (2018) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2018.3764 · Cited by 162
“Notably, when E-cadherin is deleted from the mouse intestine, the barrier function of the intestines is compromised (38), moreover, loss of E-cadherin in mouse epidermis may lead to improper localization of the key tight junctional proteins, resulting in permeable TJs and altered epidermal resistance (39).”
BackgroundPan, T.-L., Wang, P.-W., Aljuffali, I. A., Huang, C.-T., Lee, C.-W., & Fang, J.-Y. (2015) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2015.01.011 · Cited by 158
Role of epithelial–mesenchymal transition in proliferative vitreoretinopathy
Tamiya, S., & Kaplan, H. J. (2015) · Experimental Eye Research · doi:10.1016/j.exer.2015.02.008 · Cited by 160
Heijink, I. H., Brandenburg, S. M., Noordhoek, J. A., et al. (2009) · European Respiratory Journal · doi:10.1183/09031936.00065809 · Cited by 156
Mechanical Forces in the Skin: Roles in Tissue Architecture, Stability, and Function
Biggs, L. C., Kim, C. S. K., Miroshnikova, Y. A., & Wickström, S. A. (2019) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2019.06.137 · Cited by 159
“These features highlight the unique, layer-specific distribution of tension within the epidermis and the role of this tension in barrier maintenance (Rübsam et al., 2017; Tunggal et al., 2005) (Figure 1).”
BackgroundLei, Z., Maeda, T., Tamura, A., Nakamura, T., Yamazaki, Y., Shiratori, H., Yashiro, K., Tsukita, S., & Hamada, H. (2012) · Developmental Biology · doi:10.1016/j.ydbio.2012.07.005 · Cited by 151
Rübsam, M., Broussard, J. A., Wickström, S. A., Nekrasova, O. E., Green, K. J., & Niessen, C. M. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a029207 · Cited by 151
“These TJs are essential to prevent unnecessary water loss from the organism (Furuse et al. 2002; Tunggal et al. 2005), an essential feature for terrestrial life.”
BackgroundSelf-citationWeber, S., Niessen, M. T., Prox, J., Lüllmann‐Rauch, R., Schmitz, A., Schwanbeck, R., Blobel, C., Jorissen, E., Strooper, B. D., Niessen, C. M., et al. (2011) · Development · doi:10.1242/dev.055210 · Cited by 149
“…signaling and Notch-dependent target genes (Lin and Kopan, 2003; Lin et al., 2000; Nicolas et al., 2003; Pan et al., 2004; Rangarajan et al., 2001; Uyttendaele et al., 2004; Yamamoto et al., 2003) have revealed a crucial role for Notch signaling in the proper stratification and development of the…”
Self-citationBarriers and more: functions of tight junction proteins in the skin
Kirschner, N., & Brandner, J. M. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06554.x · Cited by 158
Desclozeaux, M., Venturato, J., Wylie, F. G., et al. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00097.2008 · Cited by 142
“E-cadherin is essential during development, from early embryogenesis through the later stages of organogenesis, as shown by genetic analysis in Drosophila and in knockdown mouse models (21, 38, 41).”
BackgroundChen, A., Beetham, H. G., Black, M. A., Priya, R., Telford, B. J., Guest, J., Wiggins, G. A. R., Godwin, T. D., Yap, A. S., & Guilford, P. (2014) · BMC Cancer · doi:10.1186/1471-2407-14-552 · Cited by 140
“Similarly, the targeted loss of E-cadherin from murine skin epithelium is also not associated with a significant loss of cell-cell adhesion, an effect attributed to compensatory upregulation of P-cadherin and desmosomal cadherin in the basal layer [32,33].”
BackgroundThe challenges of abundance: epithelial junctions and small GTPase signalling
Braga, V. M. M., & Yap, A. S. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.08.012 · Cited by 146
“Interestingly, inappropriate localization and activation of Rac in E-cadherin-null skin is also a potential cause of impairment in tight junction function and biogenesis [11 ].”
BackgroundTight junctions form a barrier in human epidermis
Kirschner, N., Houdek, P., Fromm, M., Moll, I., & Brandner, J. M. (2010) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2010.07.010 · Cited by 139
Self-citationLoss of liver E-cadherin induces sclerosing cholangitis and promotes carcinogenesis
Nakagawa, H., Hikiba, Y., Hirata, Y., Font-Burgada, J., Sakamoto, K., Hayakawa, Y., Taniguchi, K., Umemura, A., Kinoshita, H., Sakitani, K., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1322731111 · Cited by 133
“Conditional knockout of E-cadherin in skin impairs an epidermal water-barrier function that leads to perinatal lethality (4).”
BackgroundMicroRNAs in skin and wound healing
Banerjee, J., Chan, Y. C., & Sen, C. K. (2010) · Physiological Genomics · doi:10.1152/physiolgenomics.00157.2010 · Cited by 139
New insights into cadherin function in epidermal sheet formation and maintenance of tissue integrity
Tinkle, C. L., Pasolli, H. A., Stokes, N., & Fuchs, E. V. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807374105 · Cited by 138
“Interestingly, cadherin-deficient epidermis displayed defective localization of Par3, aPKC, and Scribble (Fig.”
BackgroundInfluentialYang, J., Meyer, M., Müller, A., Böhm, F., Grose, R. P., Dauwalder, T., Verrey, F., Köpf, M., Partanen, J. M., Bloch, W., et al. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.200910126 · Cited by 136
“Duplicate determinations were performed for each sample.”
Epithelial Cell Adhesion Molecule (EpCAM) Regulates Claudin Dynamics and Tight Junctions
Wu, C.-J., Mannan, P., Lu, M., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.457499 · Cited by 132
“Adherens junctions are also required for TJ formation (32).”
BackgroundAirway epithelial barrier function regulates the pathogenesis of allergic asthma
Heijink, I. H., Nawijn, M. C., & Hackett, T. (2014) · Clinical & Experimental Allergy · doi:10.1111/cea.12296 · Cited by 127
Vocal Fold Epithelial Barrier in Health and Injury: A Research Review
Erickson, E., Leydon, C., & Thibeault, S. L. (2014) · Journal of Speech Language and Hearing Research · doi:10.1044/2014_jslhr-s-13-0283 · Cited by 132
Heijink, I. H., van Oosterhout, A. J. M., & Kapùs, A. (2010) · European Respiratory Journal · doi:10.1183/09031936.00125809 · Cited by 125
Ohnemus, U., Kohrmeyer, K., Houdek, P., Rohde, H., Wladykowski, E., Vidal, S., Horstkotte, M. A., Aepfelbacher, M., Kirschner, N., Behne, M. J., et al. (2008) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5701070 · Cited by 124
Derr, K., Zou, J., Luo, K., Song, M. J., Sittampalam, G. S., Zhou, C., Michael, S., Ferrer, M., & Derr, P. (2019) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2018.0318 · Cited by 120
Kida, N., Sokabe, T., Kashio, M., Haruna, K., Mizuno, Y., Suga, Y., Nishikawa, K., Kanamaru, A., Hongo, M., Oba, A., et al. (2012) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-012-1081-3 · Cited by 121
“lacking E-cadherin, the main component of the AJ complex, specifically in the developing epidermis had a phenotype similar to the claudin-1-deficient mice [36].”
Kása, A., Csoŕtos, C., & Verin, A. D. (2014) · Tissue Barriers · doi:10.4161/21688370.2014.974448 · Cited by 122
“AJs assembly precedes tight junction formation and in some in vivo cases cadherin is required for the formation of TJs, as it controls the recruitment of ZO-1 to TJ complexes.(138) Up-regulation of ECspecific claudin-5 isoform is involved in EC barrier enhancement in some, but not all models.”
BackgroundLi, W., Chen, Z., Chin, I., Chen, Z., & Dai, H. (2018) · Current Neuropharmacology · doi:10.2174/1570159x16666180222164809 · Cited by 122
“The deletion of VE-cadherin in mice disrupted TJ integrity and altered localization of ZO-1, claudin-1, and claudin-4 by activating Rac and protein kinase C [61].”
BackgroundE-cadherin Beyond Structure: A Signaling Hub in Colon Homeostasis and Disease
Daulagala, A. C., Bridges, C., & Kourtidis, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20112756 · Cited by 130
“Importantly, E-cadherin is required for TJs and tissue barrier formation [20,21].”
BackgroundTight junction proteins in keratinocytes: localization and contribution to barrier function
Yuki, T., Haratake, A., Koishikawa, H., Morita, K., Miyachi, Y., & Inoue, S. (2007) · Experimental Dermatology · doi:10.1111/j.1600-0625.2006.00539.x · Cited by 117
Ciccocioppo, R., Finamore, A., Ara, C., Sabatino, A. D., Mengheri, E., & Corazza, G. R. (2006) · American Journal of Clinical Pathology · doi:10.1309/dtyr-a91g-8r0k-tm8m · Cited by 116
Role of aPKC Isoforms and Their Binding Partners Par3 and Par6 in Epidermal Barrier Formation
Helfrich, I., Schmitz, A., Zigrino, P., Michels, C., Haase, I., Bivic, A. L., Leitges, M., & Niessen, C. M. (2006) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700621 · Cited by 115
“Interestingly, in the granular layer a highly concentrated staining was observed at lateral intercellular borders, which is reminiscent of the distribution of several tight junctional markers in the skin (Tunggal et al., 2005).”
BackgroundMethodResultInfluentialSelf-citationCell Adhesion in Epidermal Development and Barrier Formation
Sumigray, K., & Lechler, T. (2015) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2014.11.027 · Cited by 116
“It is also becoming increasingly clear that not only does each cell–cell junction have its own independent functions, but also that there is crosstalk and interplay between the various junctional complexes that is important to give the epidermis full barrier activity (Godsel et al., 2010; Lewis et al., 1997; Sumigray,…”
BackgroundInfluentialSchamberger, A. C., Miše, N., Jia, J., Genoyer, E., Yildirim, A. Ö., Meiners, S., & Eickelberg, O. (2014) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2013-0090oc · Cited by 111
mTORC1 and mTORC2 regulate skin morphogenesis and epidermal barrier formation
Ding, X., Bloch, W., Iden, S., Rüegg, M. A., Hall, M. N., Leptin, M., Partridge, L., & Eming, S. A. (2016) · Nature Communications · doi:10.1038/ncomms13226 · Cited by 122
A rapidly prototyped lung-on-a-chip model using 3D-printed molds
Shrestha, J., Ghadiri, M., Shanmugavel, M., Bazaz, S. R., Vasilescu, S. A., Ding, L., & Warkiani, M. E. (2019) · Organs-on-a-Chip · doi:10.1016/j.ooc.2020.100001 · Cited by 113
Dynamics and Regulation of Epithelial Adherens Junctions
Ivanov, A. I., & Naydenov, N. G. (2013) · International review of cytology · doi:10.1016/b978-0-12-407697-6.00002-7 · Cited by 115
“Instead, it caused the increased paracellular permeability and hyperproliferation of keratinocytes (Tinkle et al., 2004; Tunggal et al., 2005).”
BackgroundAcharya, B. R., Wu, S. K., Lieu, Z. Z., Parton, R. G., Grill, S. W., Bershadsky, A. D., Gomez, G. A., & Yap, A. S. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.02.078 · Cited by 110
Barki, K. G., Das, A., Dixith, S., Ghatak, P. D., Mathew‐Steiner, S. S., Schwab, E. R., Khanna, S., Wozniak, D. J., Roy, S., & Sen, C. K. (2017) · Annals of Surgery · doi:10.1097/sla.0000000000002504 · Cited by 109
“E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions.(20) Study of mechanistic underpinnings recognized cutaneous wound-edge miR-9 as being biofilminducible.”
Jia, Y., Hu, J., An, K., Zhao, Q., Dang, Y., Liu, H., Zhao, W., Geng, S., & Xu, F. (2023) · Nature Communications · doi:10.1038/s41467-023-38209-x · Cited by 115
“E-cadherin is a major component of epidermal intercellular junctions, and its loss of expression correlates with impaired epidermal cell function and morphology 46 .”
Two-Path Impedance Spectroscopy for Measuring Paracellular and Transcellular Epithelial Resistance
Krug, S. M., Fromm, M., & Günzel, D. (2009) · Biophysical Journal · doi:10.1016/j.bpj.2009.08.003 · Cited by 106
Self-citationTight junctions in skin inflammation
Bäsler, K., & Brandner, J. M. (2016) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-016-1903-9 · Cited by 111
Jensen, J., Pfeiffer, S., Witt, M., Bräutigam, M., Neumann, C., Weichenthal, M., Schwarz, T., Fölster‐Holst, R., & Proksch, E. (2009) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.03.032 · Cited by 107
Tight Junction Proteins Claudin-1 and Occludin Are Important for Cutaneous Wound Healing
Volksdorf, T., Heilmann, J., Eming, S. A., Schawjinski, K., Zorn‐Kruppa, M., Ueck, C., Vidal‐y‐Sy, S., Windhorst, S., Jücker, M., Moll, I., et al. (2017) · American Journal Of Pathology · doi:10.1016/j.ajpath.2017.02.006 · Cited by 102
Dual role of E-cadherin in cancer cells
Rubtsova, S. N., Zhitnyak, I. Y., & Gloushankova, N. A. (2021) · Tissue Barriers · doi:10.1080/21688370.2021.2005420 · Cited by 104
E-cadherin is required for intestinal morphogenesis in the mouse
Bondow, B. J., Faber, M. L., Wojta, K. J., Walker, E. M., & Battle, M. A. (2012) · Developmental Biology · doi:10.1016/j.ydbio.2012.06.005 · Cited by 98
Aono, S., & Hirai, Y. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.08.012 · Cited by 95
Rezaee, F., Meednu, N., Emo, J. A., Saatian, B., Chapman, T. J., Naydenov, N. G., Benedetto, A. D., Beck, L. A., Ivanov, A. I., & Georas, S. N. (2011) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2011.08.035 · Cited by 100
“41,57-59 Surprisingly, our results ruled out a role for NM II in polyI:C-induced disassembly of apical junctions in our model's airway epithelial cells (1) because polyI:C did not trigger formation of contractile actomyosin structures, such as apical rings or vacuoles and (2) because pharmacologic inhibition of NM II…”
BackgroundResultTiam1 takes PARt in cell polarity
Mertens, A. E. E., Pegtel, D. M., & Collard, J. G. (2006) · Trends in Cell Biology · doi:10.1016/j.tcb.2006.04.001 · Cited by 97
Glycated Reconstructed Human Skin as a Platform to Study the Pathogenesis of Skin Aging
Pennacchi, P. C., de Almeida, M. E. S., Gomes, O. L. A., Faião‐Flores, F., Crepaldi, M. C. D. A., dos Santos, M. F., Barros, S. B. D. M., & Maria–Engler, S. S. (2015) · Tissue Engineering Part A · doi:10.1089/ten.tea.2015.0009 · Cited by 96
“32 In vitro studies have shown that E-cadherin is not only necessary for adherent junction’s formation, but its adhesive activity is also crucial for the assembly of other junctional complexes such as desmosomes, gap junctions, and tight junctions.”
InfluentialCaraballo, J. C., Yshii, C., Westphal, W., Moninger, T. O., & Comellas, A. P. (2010) · Respirology · doi:10.1111/j.1440-1843.2010.01910.x · Cited by 96
Regmi, S. C., Park, S., Ku, S., & Kim, J. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.02.003 · Cited by 93
Tight Junction Proteins in the Skin
Brandner, J. M., Kief, S., Wladykowski, E., Houdek, P., & Moll, I. (2006) · Skin Pharmacology and Physiology · doi:10.1159/000091973 · Cited by 93
“Electron microscopy studies in claudin 6 transgenic mice have not yet been published.Epidermis-specific E-cadherin knockout mice demonstrate the interaction of AJ and TJ in the skin [”
BackgroundReischauer, S., Levesque, M. P., Nüsslein‐Volhard, C., & Sonawane, M. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000720 · Cited by 92
Wang, H., Gong, P., Chen, T., Gao, S., Wu, Z., Wang, X., Li, J., Marjani, S. L., Costa, J. C., Weissman, S. M., et al. (2021) · Advanced Science · doi:10.1002/advs.202004320 · Cited by 88
Jin, Y., Shenoy, A. K., Doernberg, S. N., Chen, H., Luo, H., Shen, H., Lin, T., Tarrash, M., Cai, Q., Hu, X., et al. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.03.037 · Cited by 87
Metadata
- Authors
- Tunggal, J. A., Helfrich, I., Schmitz, A., Schwarz, H., Günzel, D., Fromm, M., Kemler, R., Krieg, T., & Niessen, C. M.
- Affiliations
- University of Cologne (DE)
- Max Planck Institute for Developmental Biology (DE)
- Stiftung Charité (DE)
- Max Planck Society (DE)
- Corresponding author
- Niessen, Carien M
- Venue
- The EMBO Journal
- Published
- 2005-03-03
- Volume
- 24
- Issue
- 6
- Pages
- 1146-1156
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC556407
- OpenAlex
- W2145470537
- Semantic Scholar
- a188609a53de11c26fa2a5f349e10e9c4ff65cab
- Cited by
- 491
- References
- 53
- Citations by year
- 2026: 23 · 2025: 23 · 2024: 23 · 2023: 21 · 2022: 18 · 2021: 23 · 2020: 23 · 2019: 21 · 2018: 22 · 2017: 25 · 2016: 26 · 2015: 28 · 2014: 32 · 2013: 22 · 2012: 29
- FWCI
- 11.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Northwestern University
- Deutsches Krebsforschungszentrum
- Deutsche Forschungsgemeinschaft (SFB589)
- Universität zu Köln
- University of North Carolina at Chapel Hill
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- E-cadherin, skin barrier function, tight junctions, desmosomes, stratified epithelium, conditional gene inactivation, epidermal permeability, Rac, atypical protein kinase C, perinatal lethality, cell adhesion
- MeSH terms
- Animals, Cell Communication, Desmosomes, Epidermis, Genes, Lethal, Membrane Proteins, Mice, Transgenic, Protein Kinase C, Water, Cadherins, Gene Deletion, Tight Junctions, rac GTP-Binding Proteins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-27, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-27 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
