Cited by 38Hair Growth and Disordersdental development and anomaliesDevelopmental Biology and Gene Regulation

Analysis of the Temporal Requirement for Eda in Hair and Sweat Gland Development

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Cui, Chang-Yi, Kunisada, Makoto, Esibizione, Diana, Douglass, Eric G., Schlessinger, David·2009·Journal of Investigative Dermatology

Abstract

EDA signaling is important in skin appendage initiation. Its possible involvement in appendage subtype determination and postinduction stage appendage development, however, has not been studied systematically. To address these issues we manipulated Eda-A1 transgene expression in a tetracycline-regulated conditional mouse model, where the transgene is the only source of active ectodysplasin (Eda). We find that Eda-A1 restores sweat glands and all hair subtypes in Tabby, but each requires its action at an idiosyncratic time of development: by E17 for guard, by E19 for awl, and starting at E18 for zigzag/auchen hair. Guard and awl hairs were indistinguishable from their wild-type counterparts; but restored zigzag and auchen hairs, although recognizable, were somewhat smaller and lacked characteristic bends. Notably, secondary hair follicle formation of awl, auchen, and zigzag hairs required higher Eda-A1 expression level than did guard hair or sweat glands. Furthermore, Eda-A1 expression is required until the early dermal papilla stage for guard hair germs to make follicles, but is dispensable for their maturation. Similarly, sweat gland pegs require Eda-A1 at an early stage to form mature glands. Thus we infer that EDA signaling is needed for the determination and development of various skin appendages at spatiotemporally restricted intervals.

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References 46 · Cited by 38

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  1. Blanpain C Fuchs E 2006 Epidermal stem cells of the skin Annu Rev Cell Dev Biol 22 339 373 16824012 PMC2405915
  2. Botchkarev VA Paus R 2003 Molecular biology of hair morphogenesis: development and cycling J Exp Zoolog B Mol Dev Evol 298 164 180 12949776
  3. Casal ML Lewis JR Mauldin EA Tardivel A Ingold K Favre M 2007 Significant correction of disease after postnatal administration of recombinant ectodysplasin A in canine X-linked ectodermal dysplasia Am J Hum Genet 81 1050 1056 17924345 PMC2265652
  4. Chiang C Swan RZ Grachtchouk M Bolinger M Litingtung Y Robertson EK 1999 Essential role for Sonic hedgehog during hair follicle morphogenesis Dev Biol 205 1 9 9882493
  5. Cui CY Durmowicz M Ottolenghi C Hashimoto T Griggs B Srivastava AK 2003 Inducible mEDA-A1 transgene mediates sebaceous gland hyperplasia and differential formation of two types of mouse hair follicles Hum Mol Genet 12 2931 2940 14506134
  6. Cui CY Smith JA Schlessinger D Chan CC 2005 X-linked anhidrotic ectodermal dysplasia disruption yields a mouse model for ocular surface disease and resultant blindness Am J Pathol 167 89 95 15972955 PMC1603450
  7. Cui CY Schlessinger D 2006 EDA signaling and skin appendage development Cell Cycle 5 2477 2483 17102627 PMC2860309
  8. Cui CY Hashimoto T Grivennikov SI Piao Y Nedospasov SA Schlessinger D 2006 Ectodysplasin regulates the lymphotoxin-beta pathway for hair differentiation Proc Natl Acad Sci U S A 103 9142 9147 16738056 PMC1482580
  9. Drew CF Lin CM Jiang TX Blunt G Mou C Chuong CM 2007 The Edar subfamily in feather placode formation Dev Biol 305 232 245 17362907 PMC2696204
  10. Durmowicz MC Cui CY Schlessinger D 2002 The EDA gene is a target of, but does not regulate Wnt signaling Gene 285 203 211 12039047
  11. Elomaa O Pulkkinen K Hannelius U Mikkola M Saarialho-Kere U Kere J 2001 Ectodysplasin is released by proteolytic shedding and binds to the EDAR protein Hum Mol Genet 10 953 962 11309369
  12. Ezer S Bayes M Elomaa O Schlessinger D Kere J 1999 Ectodysplasin is a collagenous trimeric type II membrane protein with a tumor necrosis factor-like domain and co-localizes with cytoskeletal structures at lateral and apical surfaces of cells Hum Mol Genet 8 2079 2086 10484778
  13. Fessing MY Sharova TY Sharov AA Atoyan R Botchkarev VA 2006 Involvement of the Edar signaling in the control of hair follicle involution (catagen) Am J Pathol 169 2075 2084 17148670 PMC1762472
  14. Fujimoto A Kimura R Ohashi J Omi K Yuliwulandari R Batubara L 2007 A scan for genetic determinants of human hair morphology: EDAR is associated with Asian hair thickness Hum Mol Genet In press 18065779
  15. Gaide O Schneider P 2003 Permanent correction of an inherited ectodermal dysplasia with recombinant EDA Nat Med 9 614 618 12692542
  16. Hammerschmidt B Schlake T 2007 Localization of Shh expression by Wnt and Eda affects axial polarity and shape of hairs Dev Biol 305 246 261 17376426
  17. Hardy MH 1992 The secret life of the hair follicle Trends Genet 8 55 61 1566372
  18. Hashimoto T Schlessinger D Cui CY 2008 Troy binding to lymphotoxin-α activates NF-kB mediated transcription Cell Cycle 7 106 111 18202551
  19. Headon DJ Overbeek PA 1999 Involvement of a novel Tnf receptor homologue in hair follicle induction Nat Genet 22 370 374 10431242
  20. Hennighausen L Wall RJ Tillmann U Li M Furth PA 1995 Conditional gene expression in secretory tissues and skin of transgenic mice using the MMTV-LTR and the tetracycline responsive system J Cell Biochem 59 463 472 8749716
  21. Klein NC Cunha BA 1995 Tetracyclines Med Clin North Am 79 789 801 7791423
  22. Knecht AK Hosemann KE Kingsley DM 2007 Constraints on utilization of the EDA-signaling pathway in threespine stickleback evolution Evol Dev 9 141 154 17371397
  23. Laurikkala J Pispa J Jung HS Nieminen P Mikkola M Wang X 2002 Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor Edar Development 129 2541 2553 11973284
  24. Muller-Rover S Handjiski B van der Veen C Eichmuller S Foitzik K McKay IA 2001 A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages J Invest Dermatol 117 3 15 11442744
  25. Mustonen T Pispa J Mikkola ML Pummila M Kangas AT Pakkasjarvi L 2003 Stimulation of ectodermal organ development by Ectodysplasin-A1 Dev Biol 259 123 136 12812793
  26. Mustonen T Ilmonen M Pummila M Kangas AT Laurikkala J Jaatinen R 2004 Ectodysplasin A1 promotes placodal cell fate during early morphogenesis of ectodermal appendages Development 131 4907 4919 15371307
  27. Newton K French DM Yan M Frantz GD Dixit VM 2004 Myodegeneration in EDA-A2 transgenic mice is prevented by XEDAR deficiency Mol Cell Biol 24 1608 1613 14749376 PMC344191
  28. Pantalacci S Chaumot A Benoit G Sadier A Delsuc F Douzery EJ 2008 Conserved features and evolutionary shifts of the EDA signaling pathway involved in vertebrate skin appendage development Mol Biol Evol 25 912 928 18304980
  29. Prodi DA Pirastu N Maninchedda G Sassu A Picciau A Palmas MA 2008 EDA2R Is Associated with Androgenetic Alopecia J Invest Dermatol Epub ahead of print 18385763
  30. Pummila M Fliniaux I Jaatinen R James MJ Laurikkala J Schneider P 2007 Ectodysplasin has a dual role in ectodermal organogenesis: inhibition of Bmp activity and induction of Shh expression Development 134 117 125 17164417
  31. Schlake T 2005 Segmental Igfbp5 expression is specifically associated with the bent structure of zigzag hairs Mech Dev 122 988 997 16024235
  32. Schmidt-Ullrich R Tobin DJ Lenhard D Schneider P Paus R Scheidereit C 2006 NF-kappaB transmits Eda A1/EdaR signalling to activate Shh and cyclin D1 expression, and controls post-initiation hair placode down growth Development 133 1045 1057 16481354
  33. Shao Z Browning JL Lee X Scott ML Shulga-Morskaya S Allaire N 2005 TAJ/TROY, an orphan TNF receptor family member, binds Nogo-66 receptor 1 and regulates axonal regeneration Neuron 45 353 359 15694322
  34. Sick S Reinker S Timmer J Schlake T 2006 WNT and DKK determine hair follicle spacing through a reaction-diffusion mechanism Science 314 1447 1450 17082421
  35. Srivastava AK Pispa J Hartung AJ Du Y Ezer S Jenks T 1997 The Tabby phenotype is caused by mutation in a mouse homologue of the EDA gene that reveals novel mouse and human exons and encodes a protein (ectodysplasin-A) with collagenous domains Proc Natl Acad Sci U S A 94 13069 13074 9371801 PMC24264
  36. Srivastava AK Durmowicz MC Hartung AJ Hudson J Ouzts LV Donovan DM 2001 Ectodysplasin-A1 is sufficient to rescue both hair growth and sweat glands in Tabby mice Hum Mol Genet 10 2973 2981 11751679
  37. St-Jacques B Dassule HR Karavanova I Botchkarev VA Li J Danielian PS 1998 Sonic hedgehog signaling is essential for hair development Curr Biol 8 1058 1068 9768360
  38. Vielkind U Hardy MH 1996 Changing patterns of cell adhesion molecules during mouse pelage hair follicle development. 2. Follicle morphogenesis in the hair mutants, Tabby and downy Acta Anat (Basel) 157 183 194 9226037
  39. Yan M Wang LC Hymowitz SG Schilbach S Lee J Goddard A 2000 Two-amino acid molecular switch in an epithelial morphogen that regulates binding to two distinct receptors Science 290 523 527 11039935
  40. Zhang M Brancaccio A Weiner L Missero C Brissette JL 2003 Ectodysplasin regulates pattern formation in the mammalian hair coat Genesis 37 30 37 14502575

Authors
Cui, C.-Y., Kunisada, M., Esibizione, D., Douglass, E. G., & Schlessinger, D.
Affiliations
National Institutes of Health (US)
Corresponding author
Schlessinger, David
Venue
Journal of Investigative Dermatology
Publisher
Elsevier BV
Published
2009-04
Volume
129
Issue
4
Pages
984-993
ISSN
0022-202X (ISSN-L)
OpenAlex
W1972593475
Cited by
38
References
46
Citations by year
2026: 3 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 1 · 2016: 2 · 2015: 3 · 2014: 6 · 2013: 1
FWCI
3.22
Type
journal article
Language
en
Open access
Locations
  • Journal of Investigative Dermatology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (Z01AG000643)
Topics
  • Health Sciences › Medicine › Urology › Hair Growth and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
ectodysplasin, sweat gland development, hair follicle development, guard hair, dermal papilla, conditional mouse model
MeSH terms
Animals, Doxycycline, Female, Male, Mice, Inbred C57BL, Mice, Transgenic, Sweat Glands, Signal Transduction, Hair Follicle, Transgenes, Mice, Ectodysplasins

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