Conditional targeting of E-cadherin in skin: Insights into hyperproliferative and degenerative responses
Open accessAbstract
Loss of E-cadherin has been associated with human cancers, and yet in the early mouse embryo and the lactating mammary gland, the E-cadherin null state results in tissue dysfunction and cell death. Here we targeted loss of E-cadherin in skin epithelium. The epidermal basal layer responded by elevating P-cadherin, enabling these cells to maintain adherens junctions. Suprabasal layers upregulated desmosomal cadherins, but without classical cadherins, terminal differentiation was impaired. Progressive hyperplasia developed with age, a possible consequence of proliferative maintenance in basal cells coupled with defects in terminal differentiation. In contrast, hair follicles lost integrity of the inner root sheath and hair cuticle without apparent elevation of cadherins. These findings suggest that, if no compensatory mechanisms exist, E-cadherin loss may be incompatible with epithelial tissue survival, whereas partial compensation can result in alterations in differentiation and proliferation.
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Both blistering and overgrowth phenotypes are not observed in K14-Cre/Ecad Fl/À mice.
“Both phenotypes are not observed in K14-Cre/Ecad Fl/À mice (Young et al, 2003;Tinkle et al, 2004;this paper).”
From E‐cadherin is essential for in vivo epidermal barrier function by regulating tight junctions (2005) · cites this paper as Tinkle et al, 2004
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)
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Experimental — accuracy not yet measuredNo difference in localization of desmosomal markers plakoglobin, desmocollin 2 and desmoglein 1/2 was observed between control and E-cadherin mutant mice.
“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).”
From E‐cadherin is essential for in vivo epidermal barrier function by regulating tight junctions (2005) · cites this paper as Tinkle et al, 2004
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)
Experimental — accuracy not yet measuredThese authors did observe a slight disturbance in the epidermal barrier but have not examined tight junctional markers and function.
“Nevertheless, these authors did observe a slight disturbance in the epidermal barrier but have not examined tight junctional markers and function.”
From E‐cadherin is essential for in vivo epidermal barrier function by regulating tight junctions (2005) · cites this paper as Tinkle et al, 2004
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)
Experimental — accuracy not yet measuredThis 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.
“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).”
From E‐cadherin is essential for in vivo epidermal barrier function by regulating tight junctions (2005) · cites this paper as Tinkle et al, 2004
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.
“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).”
From E‐cadherin is essential for in vivo epidermal barrier function by regulating tight junctions (2005) · cites this paper as Tinkle et al, 2004
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References 31 · Cited by 193
Research works printed but not linked: 1
- [18]Bierkamp, C., Schwarz, H., Huber, O. & Kemler, R. (1999) Development (Cambridge, U.K.) 126, 371-381.
- Authors
- Tinkle, C. L., Lechler, T., Pasolli, H. A., & Fuchs, E.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Fuchs, Elaine
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-01-02
- Volume
- 101
- Issue
- 2
- Pages
- 552-557
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC327185
- OpenAlex
- W2127711467
- Cited by
- 193
- References
- 31
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 5 · 2019: 8 · 2018: 1 · 2017: 12 · 2016: 4 · 2015: 7 · 2014: 16 · 2013: 11 · 2012: 10
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (AR27883)
- Langley Research Center
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR027883, R37AR027883)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Keywords
- E-cadherin, conditional knockout, skin epithelium, epidermis, adherens junctions, desmosomal cadherins, terminal differentiation, hyperplasia, hair follicle, inner root sheath, compensatory mechanisms
- MeSH terms
- Animals, Microscopy, Electron, Skin, Cadherins, Mice
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