CoChat
Sign Up
Cited by 32Skin and Cellular Biology ResearchDevelopmental Biology and Gene RegulationCell Adhesion Molecules Research

Desmoplakin is required for epidermal integrity and morphogenesis in the Xenopus laevis embryo

Open access
Bharathan, Navaneetha Krishnan, Dickinson, Amanda J.G.·2019·Developmental Biology
DOI 10.1016/j.ydbio.2019.03.010PMC PMC6659752

Published version of a preprint

Open this paper in CoChat — free account

Abstract

Desmoplakin (Dsp) is a unique and critical desmosomal protein, that is integral to epidermal development. However, it is unclear whether this protein is required specifically for epidermal morphogenesis. Using morpholinos or Crispr/Cas9 mutagenesis we decreased the function of Dsp in frog embryos to better understand its role during epidermal development. Dsp morphant and mutant embryos had developmental defects such as epidermal fragility that mimicked what has been reported in mammals. Most importantly, we also uncovered a novel function for Dsp in the morphogenesis of the epidermis in X. laevis. In particular, Dsp is required during the process of radial intercalation where basally located cells move into the outer epidermal layer. Once inserted these newly intercalated cells expand their apical surface and then they differentiate into specific epidermal cell types. Decreased levels of Dsp resulted in the failure of the radially intercalating cells to expand their apical surface, thereby reducing the number of differentiated multiciliated and secretory cells. Such defects correlate with changes in E-cadherin levels and actin and microtubule localization which could explain the defects in apical expansion. A mutated form of Dsp that maintains cell-cell adhesion but eliminates the connections to the cytoskeleton results in the same epidermal morphogenesis defect. These results suggest a specific role for Dsp in the apical expansion of cells during radial intercalation. We have developed a novel system, in the frog, to demonstrate for the first time that desmosomes not only protect against mechanical stress but are also critical for epidermal morphogenesis.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.ydbio.2019.03.010

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 72

  1. Al-Jassar C, Knowles T, Jeeves M, Kami K, Behr E, Bikker H, Overduin M, Chidgey M, 2011 The nonlinear structure of the desmoplakin plakin domain and the effects of cardiomyopathy-linked mutations. J Mol Biol 411, 1049– 1061. 21756917
  2. Berika M, Garrod D, 2014 Desmosomal adhesion in vivo. Cell Commun Adhes 21, 65– 75. 24460202
  3. Bhattacharya D, Marfo CA, Li D, Lane M, Khokha MK, 2015 CRISPR/Cas9: An inexpensive, efficient loss of function tool to screen human disease genes in Xenopus. Dev Biol 408, 196– 204. 26546975 PMC4684459
  4. Billett FS, Gould RP, 1971 Fine structural changes in the differentiating epidermis of Xenopus laevis embryos. J Anat 108, 465– 480. 5575314 PMC1234183
  5. Blum M, De Robertis EM, Wallingford JB, Niehrs C, 2015 Morpholinos: Antisense and Sensibility. Dev Cell 35, 145– 149. 26506304
  6. Borysenko JZ, Revel JP, 1973 Experimental manipulation of desmosome structure. Am J Anat 137, 403– 421. 4199777
  7. Celentano A, Mignogna MD, McCullough M, Cirillo N, 2017 Pathophysiology of the Desmo-Adhesome. J Cell Physiol 232, 496– 505. 27505028
  8. Cheng X, Den Z, Koch PJ, 2005 Desmosomal cell adhesion in mammalian development. Eur J Cell Biol 84, 215– 223. 15819402
  9. Chung MI, Peyrot SM, LeBoeuf S, Park TJ, McGary KL, Marcotte EM, Wallingford JB, 2012 RFX2 is broadly required for ciliogenesis during vertebrate development. Dev Biol 363, 155– 165. 22227339 PMC3640985
  10. Delva E, Tucker DK, Kowalczyk AP, 2009 The desmosome. Cold Spring Harb Perspect Biol 1, a002543. 20066089 PMC2742091
  11. DeMarais AA, Moon RT, 1992 The armadillo homologs beta-catenin and plakoglobin are differentially expressed during early development of Xenopus laevis. Dev Biol 153, 337– 346. 1397690
  12. Dickinson AJ, Sive H, 2006 Development of the primary mouth in Xenopus laevis. Dev Biol 295, 700– 713. 16678148
  13. Dickinson AJ, Sive HL, 2009 The Wnt antagonists Frzb-1 and Crescent locally regulate basement membrane dissolution in the developing primary mouth. Development 136, 1071– 1081. 19224982 PMC2685928
  14. Drysdale TA, Elinson RP, 1992 Cell Migration and Induction in the Development of the Surface Ectodermal Pattern of the Xenopus laevis Tadpole. Development, Growth & Differentiation 34, 51– 59. 37282162
  15. Dubaissi E, Rousseau K, Lea R, Soto X, Nardeosingh S, Schweickert A, Amaya E, Thornton DJ, Papalopulu N, 2014 A secretory cell type develops alongside multiciliated cells, ionocytes and goblet cells, and provides a protective, anti-infective function in the frog embryonic mucociliary epidermis. Development 141, 1514– 1525. 24598166 PMC3957375
  16. Dusek RL, Godsel LM, Green KJ, 2007 Discriminating roles of desmosomal cadherins: beyond desmosomal adhesion. J Dermatol Sci 45, 7– 21. 17141479
  17. Eisen JS, Smith JC, 2008 Controlling morpholino experiments: don’t stop making antisense. Development 135, 1735– 1743. 18403413
  18. Farquhar MG, Palade GE, 1965 Cell junctions in amphibian skin. J Cell Biol 26, 263– 291. 5859021 PMC2106698
  19. Favre B, Begre N, Borradori L, 2018 A recessive mutation in the DSP gene linked to cardiomyopathy, skin fragility and hair defects impairs the binding of desmoplakin to epidermal keratins and the muscle-specific intermediate filament desmin. Br J Dermatol 179, 797– 799. 29878302
  20. Fleming TP, Garrod DR, Elsmore AJ, 1991 Desmosome biogenesis in the mouse preimplantation embryo. Development 112, 527– 539. 1794321
  21. Gallicano GI, Bauer C, Fuchs E, 2001 Rescuing desmoplakin function in extra-embryonic ectoderm reveals the importance of this protein in embryonic heart, neuroepithelium, skin and vasculature. Development 128, 929– 941. 11222147
  22. Gallicano GI, Kouklis P, Bauer C, Yin M, Vasioukhin V, Degenstein L, Fuchs E, 1998 Desmoplakin is required early in development for assembly of desmosomes and cytoskeletal linkage. J Cell Biol 143, 2009– 2022. 9864371 PMC2175222
  23. Garrod D, Chidgey M, 2008 Desmosome structure, composition and function. Biochim Biophys Acta 1778, 572– 587. 17854763
  24. Garrod DR, Berika MY, Bardsley WF, Holmes D, Tabernero L, 2005 Hyper-adhesion in desmosomes: its regulation in wound healing and possible relationship to cadherin crystal structure. J Cell Sci 118, 5743– 5754. 16303847
  25. Goonesinghe A, Luan XM, Hurlstone A, Garrod D, 2012 Desmosomal cadherins in zebrafish epiboly and gastrulation. BMC Dev Biol 12, 1. 22235774 PMC3268089
  26. Green KJ, Gaudry CA, 2000 Are desmosomes more than tethers for intermediate filaments? Nat Rev Mol Cell Biol 1, 208– 216. 11252896
  27. Green KJ, Parry DA, Steinert PM, Virata ML, Wagner RM, Angst BD, Nilles LA, 1990 Structure of the human desmoplakins. Implications for function in the desmosomal plaque. J Biol Chem 265, 11406– 11407. 2391353
  28. Green KJ, Simpson CL, 2007 Desmosomes: new perspectives on a classic. J Invest Dermatol 127, 2499– 2515. 17934502
  29. Harris TJ, Tepass U, 2010 Adherens junctions: from molecules to morphogenesis. Nat Rev Mol Cell Biol 11, 502– 514. 20571587
  30. Heasman J, 2002 Morpholino oligos: making sense of antisense? Dev Biol 243, 209– 214. 11884031
  31. Holbrook KA, Odland GF, 1975 The fine structure of developing human epidermis: light, scanning, and transmission electron microscopy of the periderm. J Invest Dermatol 65, 16– 38. 168272
  32. Houssin NS, Bharathan NK, Turner SD, Dickinson AJ, 2017 Role of JNK during buccopharyngeal membrane perforation, the last step of embryonic mouth formation. Dev Dyn 246, 100– 115. 28032936 PMC5261731
  33. Johnson JL, Najor NA, Green KJ, 2014 Desmosomes: regulators of cellular signaling and adhesion in epidermal health and disease. Cold Spring Harb Perspect Med 4, a015297. 25368015 PMC4208714
  34. Kim K, Lake BB, Haremaki T, Weinstein DC, Sokol SY, 2012 Rab11 regulates planar polarity and migratory behavior of multiciliated cells in Xenopus embryonic epidermis. Dev Dyn 241, 1385– 1395. 22778024 PMC4009926
  35. Kim SK, Zhang S, Werner ME, Brotslaw EJ, Mitchell JW, Altabbaa MM, Mitchell BJ, 2018 CLAMP/Spef1 regulates planar cell polarity signaling and asymmetric microtubule accumulation in the Xenopus ciliated epithelia. J Cell Biol 217, 1633– 1641. 29514918 PMC5940297
  36. Klymkowsky MW, Shook DR, Maynell LA, 1992 Evidence that the deep keratin filament systems of the Xenopus embryo act to ensure normal gastrulation. Proc Natl Acad Sci U S A 89, 8736– 8740. 1382297 PMC49995
  37. Kofron M, Heasman J, Lang SA, Wylie CC, 2002 Plakoglobin is required for maintenance of the cortical actin skeleton in early Xenopus embryos and for cdc42-mediated wound healing. J Cell Biol 158, 695– 708. 12186853 PMC2174016
  38. Kofron M, Spagnuolo A, Klymkowsky M, Wylie C, Heasman J, 1997 The roles of maternal alpha-catenin and plakoglobin in the early Xenopus embryo. Development 124, 1553– 1560. 9108371
  39. Lechler T, Fuchs E, 2007 Desmoplakin: an unexpected regulator of microtubule organization in the epidermis. J Cell Biol 176, 147– 154. 17227889 PMC2063934
  40. Lowndes M, Rakshit S, Shafraz O, Borghi N, Harmon RM, Green KJ, Sivasankar S, Nelson WJ, 2014 Different roles of cadherins in the assembly and structural integrity of the desmosome complex. J Cell Sci 127, 2339– 2350. 24610950 PMC4021477
  41. Mashal RD, Koontz J, Sklar J, 1995 Detection of mutations by cleavage of DNA heteroduplexes with bacteriophage resolvases. Nat Genet 9, 177– 183. 7719346
  42. Mitchell B, Stubbs JL, Huisman F, Taborek P, Yu C, Kintner C, 2009 The PCP pathway instructs the planar orientation of ciliated cells in the Xenopus larval skin. Curr Biol 19, 924– 929. 19427216 PMC2720401
  43. Moftah H, Dias K, Apu EH, Liu L, Uttagomol J, Bergmeier L, Kermorgant S, Wan H, 2017 Desmoglein 3 regulates membrane trafficking of cadherins, an implication in cell-cell adhesion. Cell adhesion & migration 11, 211– 232. 27254775 PMC5479455
  44. Munoz WA, Kloc M, Cho K, Lee M, Hofmann I, Sater A, Vleminckx K, McCrea PD, 2012 Plakophilin-3 is required for late embryonic amphibian development, exhibiting roles in ectodermal and neural tissues. PLoS One 7, e34342. 22496792 PMC3320641
  45. Nakayama T, Fish MB, Fisher M, Oomen-Hajagos J, Thomsen GH, Grainger RM, 2013 Simple and efficient CRISPR/Cas9-mediated targeted mutagenesis in Xenopus tropicalis. Genesis 51, 835– 843. 24123613 PMC3947545
  46. Nishimura R, Kato K, Fujiwara S, Ohashi K, Mizuno K, 2018 Solo and Keratin Filaments Regulate Epithelial Tubule Morphology. Cell Struct Funct 43, 95– 105. 29709890
  47. Nishimura T, Takeichi M, 2009 Remodeling of the adherens junctions during morphogenesis. Current topics in developmental biology 89, 33– 54. 19737641
  48. Ossipova O, Chu CW, Fillatre J, Brott BK, Itoh K, Sokol SY, 2015 The involvement of PCP proteins in radial cell intercalations during Xenopus embryonic development. Dev Biol 408, 316– 327. 26079437 PMC4810801
  49. Park TJ, Mitchell BJ, Abitua PB, Kintner C, Wallingford JB, 2008 Dishevelled controls apical docking and planar polarization of basal bodies in ciliated epithelial cells. Nat Genet 40, 871– 879. 18552847 PMC2771675
  50. Ramms L, Fabris G, Windoffer R, Schwarz N, Springer R, Zhou C, Lazar J, Stiefel S, Hersch N, Schnakenberg U, Magin TM, Leube RE, Merkel R, Hoffmann B, 2013 Keratins as the main component for the mechanical integrity of keratinocytes. Proc Natl Acad Sci U S A 110, 18513– 18518. 24167246 PMC3831947
  51. Sedzinski J, Hannezo E, Tu F, Biro M, Wallingford JB, 2016 Emergence of an Apical Epithelial Cell Surface In Vivo. Dev Cell 36, 24– 35. 26766441 PMC4735878
  52. Sedzinski J, Hannezo E, Tu F, Biro M, Wallingford JB, 2017 RhoA regulates actin network dynamics during apical surface emergence in multiciliated epithelial cells. J Cell Sci 130, 420– 428. 28089989 PMC5278671
  53. Seltmann K, Fritsch AW, Kas JA, Magin TM, 2013 Keratins significantly contribute to cell stiffness and impact invasive behavior. Proc Natl Acad Sci U S A 110, 18507– 18512. 24167274 PMC3832002
  54. Session AM, Uno Y, Kwon T, Chapman JA, Toyoda A, Takahashi S, Fukui A, Hikosaka A, Suzuki A, Kondo M, van Heeringen SJ, Quigley I, Heinz S, Ogino H, Ochi H, Hellsten U, Lyons JB, Simakov O, Putnam N, Stites J, Kuroki Y, Tanaka T, Michiue T, Watanabe M, Bogdanovic O, Lister R, Georgiou G, Paranjpe SS, van Kruijsbergen I, Shu S, Carlson J, Kinoshita T, Ohta Y, Mawaribuchi S, Jenkins J, Grimwood J, Schmutz J, Mitros T, Mozaffari SV, Suzuki Y, Haramoto Y, Yamamoto TS, Takagi C, Heald R, Miller K, Haudenschild C, Kitzman J, Nakayama T, Izutsu Y, Robert J, Fortriede J, Burns K, Lotay V, Karimi K, Yasuoka Y, Dichmann DS, Flajnik MF, Houston DW, Shendure J, DuPasquier L, Vize PD, Zorn AM, Ito M, Marcotte EM, Wallingford JB, Ito Y, Asashima M, Ueno N, Matsuda Y, Veenstra GJ, Fujiyama A, Harland RM, Taira M, Rokhsar DS, 2016 Genome evolution in the allotetraploid frog Xenopus laevis. Nature 538, 336– 343. 27762356 PMC5313049
  55. Shafraz O, Rubsam M, Stahley SN, Caldara AL, Kowalczyk AP, Niessen CM, Sivasankar S, 2018 E-cadherin binds to desmoglein to facilitate desmosome assembly. Elife 7. PMC6066328 29999492
  56. Shah AN, Moens CB, Miller AC, 2016 Targeted candidate gene screens using CRISPR/Cas9 technology. Methods Cell Biol 135, 89– 106. 27443921
  57. Smith FJ, Wilson NJ, Moss C, Dopping-Hepenstal P, McGrath J, 2012 Compound heterozygous mutations in desmoplakin cause skin fragility and woolly hair. Br J Dermatol 166, 894– 896. 21981446
  58. Sonavane PR, Wang C, Dzamba B, Weber GF, Periasamy A, DeSimone DW, 2017 Mechanical and signaling roles for keratin intermediate filaments in the assembly and morphogenesis of Xenopus mesendoderm tissue at gastrulation. Development 144, 4363– 4376. 28982683 PMC5769636
  59. Stubbs JL, Davidson L, Keller R, Kintner C, 2006 Radial intercalation of ciliated cells during Xenopus skin development. Development 133, 2507– 2515. 16728476
  60. Stubbs JL, Oishi I, Izpisua Belmonte JC, Kintner C, 2008 The forkhead protein Foxj1 specifies node-like cilia in Xenopus and zebrafish embryos. Nat Genet 40, 1454– 1460. 19011629 PMC4648715
  61. Stubbs JL, Vladar EK, Axelrod JD, Kintner C, 2012 Multicilin promotes centriole assembly and ciliogenesis during multiciliate cell differentiation. Nat Cell Biol 14, 140– 147. 22231168 PMC3329891
  62. Sumigray KD, Chen H, Lechler T, 2011 Lis1 is essential for cortical microtubule organization and desmosome stability in the epidermis. J Cell Biol 194, 631– 642. 21844209 PMC3160577
  63. Sumigray KD, Lechler T, 2011 Control of cortical microtubule organization and desmosome stability by centrosomal proteins. Bioarchitecture 1, 221– 224. 22754612 PMC3384573
  64. Sumigray KD, Lechler T, 2012 Desmoplakin controls microvilli length but not cell adhesion or keratin organization in the intestinal epithelium. Mol Biol Cell 23, 792– 799. 22238362 PMC3290639
  65. Vasioukhin V, Bowers E, Bauer C, Degenstein L, Fuchs E, 2001 Desmoplakin is essential in epidermal sheet formation. Nat Cell Biol 3, 1076– 1085. 11781569
  66. Virata ML, Wagner RM, Parry DA, Green KJ, 1992 Molecular structure of the human desmoplakin I and II amino terminus. Proc Natl Acad Sci U S A 89, 544– 548. 1731325 PMC48275
  67. Walck-Shannon E, Hardin J, 2014 Cell intercalation from top to bottom. Nat Rev Mol Cell Biol 15, 34– 48. 24355988 PMC4550482
  68. Wang F, Shi Z, Cui Y, Guo X, Shi YB, Chen Y, 2015 Targeted gene disruption in Xenopus laevis using CRISPR/Cas9. Cell Biosci 5, 15. 25897376 PMC4403895
  69. Werner ME, Mitchell JW, Putzbach W, Bacon E, Kim SK, Mitchell BJ, 2014 Radial intercalation is regulated by the Par complex and the microtubule-stabilizing protein CLAMP/Spef1. J Cell Biol 206, 367– 376. 25070955 PMC4121976
  70. Whittock NV, Ashton GH, Dopping-Hepenstal PJ, Gratian MJ, Keane FM, Eady RA, McGrath JA, 1999 Striate palmoplantar keratoderma resulting from desmoplakin haploinsufficiency. J Invest Dermatol 113, 940– 946. 10594734
  71. Whittock NV, Wan H, Morley SM, Garzon MC, Kristal L, Hyde P, McLean WH, Pulkkinen L, Uitto J, Christiano AM, Eady RA, McGrath JA, 2002 Compound heterozygosity for non-sense and mis-sense mutations in desmoplakin underlies skin fragility/woolly hair syndrome. J Invest Dermatol 118, 232– 238. 11841538
  72. Yonemura S, 2011 Cadherin-actin interactions at adherens junctions. Curr Opin Cell Biol 23, 515– 522. 21807490

Cited by

Sorted by citations

Authors
Bharathan, N. K., & Dickinson, A. J. G.
Affiliations
  • Emory University (US)
  • Virginia Commonwealth University (US)
Corresponding author
Dickinson, Amanda J.G.
ORCID
Venue
Developmental Biology
Publisher
Elsevier BV
Published
2019-06
Volume
450
Issue
2
Pages
115-131
ISSN
0012-1606 (ISSN-L)
DOI
10.1016/j.ydbio.2019.03.010
PMC
PMC6659752
OpenAlex
W2952609100
Cited by
32
References
3
Citations by year
2026: 4 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 8 · 2019: 2
FWCI
2.25
Type
journal article
Language
en
Open access
Licence
Locations
  • Developmental Biology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Science Foundation (IOS-1349668)
  • National Institutes of Health (RAR065583A)
  • NIH-NCI (P30 CA016059)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords
desmoplakin, desmosomes, epidermal morphogenesis, epidermal development, E-cadherin, actin localization, microtubules, multiciliated cells, secretory cells, Xenopus laevis embryos, cell-cell adhesion, cytoskeleton
MeSH terms
Animals, Cell Adhesion, Cell Communication, Embryo, Nonmammalian, Epidermis, Morphogenesis, Xenopus laevis, Xenopus Proteins, Desmoplakins

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.

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