Reciprocal Requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin Signaling Pathways in Hair Follicle Induction

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2009 Jul 22

PMID 19619491

Citations 195

Authors

Yuhang Zhang

Philip Tomann

Thomas Andl

Natalie M Gallant

Joerg Huelsken

Boris Jerchow

Walter Birchmeier

Ralf Paus

Stefano Piccolo

Marja L Mikkola

Edward E Morrisey

Paul A Overbeek

Claus Scheidereit

Sarah E Millar

Ruth Schmidt-Ullrich

Affiliations

Soon will be listed here.

Abstract

Wnt/beta-catenin and NF-kappaB signaling mechanisms provide central controls in development and disease, but how these pathways intersect is unclear. Using hair follicle induction as a model system, we show that patterning of dermal Wnt/beta-catenin signaling requires epithelial beta-catenin activity. We find that Wnt/beta-catenin signaling is absolutely required for NF-kappaB activation, and that Edar is a direct Wnt target gene. Wnt/beta-catenin signaling is initially activated independently of EDA/EDAR/NF-kappaB activity in primary hair follicle primordia. However, Eda/Edar/NF-kappaB signaling is required to refine the pattern of Wnt/beta-catenin activity, and to maintain this activity at later stages of placode development. We show that maintenance of localized expression of Wnt10b and Wnt10a requires NF-kappaB signaling, providing a molecular explanation for the latter observation, and identify Wnt10b as a direct NF-kappaB target. These data reveal a complex interplay and interdependence of Wnt/beta-catenin and EDA/EDAR/NF-kappaB signaling pathways in initiation and maintenance of primary hair follicle placodes.

Citing Articles

Wnt signaling modulates mechanotransduction in the epidermis to drive hair follicle regeneration.

Oak A, Bagchi A, Brukman M, Toth J, Ford J, Zheng Y Sci Adv. 2025; 11(8):eadq0638.

PMID: 39970220 PMC: 11838001. DOI: 10.1126/sciadv.adq0638.

Network analysis reveals potential mechanisms that determine the cellular identity of keratinocytes and corneal epithelial cells through the Hox/Gtl2-Dio3 miRNA axis.

Guo Y, Wu W, Chen H, Wang X, Zhang Y, Li S Front Cell Dev Biol. 2025; 13:1475334.

PMID: 39896421 PMC: 11782130. DOI: 10.3389/fcell.2025.1475334.

Embryonic Mammary Gland Morphogenesis.

Myllymaki S, Lan Q, Mikkola M Adv Exp Med Biol. 2025; 1464():9-27.

PMID: 39821018 DOI: 10.1007/978-3-031-70875-6_2.

Unlocking the genetic secrets of Dorper sheep: insights into wool shedding and hair follicle development.

Yuan X, Meng K, Wang Y, Wang Y, Pan C, Sun H Front Vet Sci. 2024; 11:1489379.

PMID: 39726582 PMC: 11670804. DOI: 10.3389/fvets.2024.1489379.

Phytochemical Compounds as Promising Therapeutics for Intestinal Fibrosis in Inflammatory Bowel Disease: A Critical Review.

Touny A, Venkataraman B, Ojha S, Pessia M, Subramanian V, Hariharagowdru S Nutrients. 2024; 16(21).

PMID: 39519465 PMC: 11547603. DOI: 10.3390/nu16213633.

References

Yu H, Jerchow B, Sheu T, Liu B, Costantini F, Puzas J . The role of Axin2 in calvarial morphogenesis and craniosynostosis. Development. 2005; 132(8):1995-2005. PMC: 1828115. DOI: 10.1242/dev.01786. View

Headon D, Overbeek P . Involvement of a novel Tnf receptor homologue in hair follicle induction. Nat Genet. 1999; 22(4):370-4. DOI: 10.1038/11943. View

Huelsken J, Vogel R, Erdmann B, Cotsarelis G, Birchmeier W . beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell. 2001; 105(4):533-45. DOI: 10.1016/s0092-8674(01)00336-1. View

Naugler W, Karin M . NF-kappaB and cancer-identifying targets and mechanisms. Curr Opin Genet Dev. 2008; 18(1):19-26. PMC: 2587362. DOI: 10.1016/j.gde.2008.01.020. View

Houghton L, Lindon C, Morgan B . The ectodysplasin pathway in feather tract development. Development. 2005; 132(5):863-72. DOI: 10.1242/dev.01651. View

Chu E, Hens J, Andl T, Kairo A, Yamaguchi T, Brisken C . Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis. Development. 2004; 131(19):4819-29. DOI: 10.1242/dev.01347. View

Yang S, Andl T, Grachtchouk V, Wang A, Liu J, Syu L . Pathological responses to oncogenic Hedgehog signaling in skin are dependent on canonical Wnt/beta3-catenin signaling. Nat Genet. 2009; 40(9):1130-5. PMC: 2688690. DOI: 10.1038/ng.192. View

Zhang M, Brancaccio A, Weiner L, Missero C, Brissette J . Ectodysplasin regulates pattern formation in the mammalian hair coat. Genesis. 2003; 37(1):30-7. DOI: 10.1002/gene.10230. View

Jho E, Zhang T, Domon C, Joo C, Freund J, Costantini F . Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol Cell Biol. 2002; 22(4):1172-83. PMC: 134648. DOI: 10.1128/MCB.22.4.1172-1183.2002. View

10.

Zhang Y, Andl T, Yang S, Teta M, Liu F, Seykora J . Activation of beta-catenin signaling programs embryonic epidermis to hair follicle fate. Development. 2008; 135(12):2161-72. PMC: 2516408. DOI: 10.1242/dev.017459. View

11.

Hardy M . The secret life of the hair follicle. Trends Genet. 1992; 8(2):55-61. DOI: 10.1016/0168-9525(92)90350-d. View

12.

Mikkola M, Pispa J, Pekkanen M, Paulin L, Nieminen P, Kere J . Ectodysplasin, a protein required for epithelial morphogenesis, is a novel TNF homologue and promotes cell-matrix adhesion. Mech Dev. 1999; 88(2):133-46. DOI: 10.1016/s0925-4773(99)00180-x. View

13.

Botchkarev V, Botchkareva N, Roth W, Nakamura M, Chen L, Herzog W . Noggin is a mesenchymally derived stimulator of hair-follicle induction. Nat Cell Biol. 1999; 1(3):158-64. DOI: 10.1038/11078. View

14.

Yan M, Wang L, Hymowitz S, Schilbach S, Lee J, Goddard A . Two-amino acid molecular switch in an epithelial morphogen that regulates binding to two distinct receptors. Science. 2000; 290(5491):523-7. DOI: 10.1126/science.290.5491.523. View

15.

Jiang T, Widelitz R, Shen W, Will P, Wu D, Lin C . Integument pattern formation involves genetic and epigenetic controls: feather arrays simulated by digital hormone models. Int J Dev Biol. 2004; 48(2-3):117-35. PMC: 4386648. View

16.

Clevers H . Wnt/beta-catenin signaling in development and disease. Cell. 2006; 127(3):469-80. DOI: 10.1016/j.cell.2006.10.018. View

17.

Maretto S, Cordenonsi M, Dupont S, Braghetta P, Broccoli V, Hassan A . Mapping Wnt/beta-catenin signaling during mouse development and in colorectal tumors. Proc Natl Acad Sci U S A. 2003; 100(6):3299-304. PMC: 152286. DOI: 10.1073/pnas.0434590100. View

18.

Schmidt-Ullrich R, Memet S, Lilienbaum A, Feuillard J, Raphael M, Israel A . NF-kappaB activity in transgenic mice: developmental regulation and tissue specificity. Development. 1996; 122(7):2117-28. DOI: 10.1242/dev.122.7.2117. View

19.

Adaimy L, Chouery E, Megarbane H, Mroueh S, Delague V, Nicolas E . Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia. Am J Hum Genet. 2007; 81(4):821-8. PMC: 1973944. DOI: 10.1086/520064. View

20.

Dasgupta R, Fuchs E . Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation. Development. 1999; 126(20):4557-68. DOI: 10.1242/dev.126.20.4557. View