QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online December 12, 2006
doi: 10.1242/10.1242/dev.02708

This Article Figures Only Full Text Full Text (PDF) Supplementary Material Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pummila, M. Articles by Mikkola, M. L. Search for Related Content PubMed PubMed Citation Articles by Pummila, M. Articles by Mikkola, M. L. Social Bookmarking                         What's this?

Ectodysplasin has a dual role in ectodermal organogenesis: inhibition of Bmp activity and induction of Shh expression

¹ Institute of Biotechnology, Developmental Biology Program, University of Helsinki, 00014 Helsinki, Finland.
² Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.

^* Authors for correspondence (e-mail: irma.thesleff{at}helsinki.fi; marja.mikkola{at}helsinki.fi)

Accepted 20 October 2006

Ectodermal organogenesis is regulated by inductive and reciprocal signalling cascades that involve multiple signal molecules in several conserved families. Ectodysplasin-A (Eda), a tumour necrosis factor-like signalling molecule, and its receptor Edar are required for the development of a number of ectodermal organs in vertebrates. In mice, lack of Eda leads to failure in primary hair placode formation and missing or abnormally shaped teeth, whereas mice overexpressing Eda are characterized by enlarged hair placodes and supernumerary teeth and mammary glands. Here, we report two signalling outcomes of the Eda pathway: suppression of bone morphogenetic protein (Bmp) activity and upregulation of sonic hedgehog (Shh) signalling. Recombinant Eda counteracted Bmp4 activity in developing teeth and, importantly, inhibition of BMP activity by exogenous noggin partially restored primary hair placode formation in Eda-deficient skin in vitro, indicating that suppression of Bmp activity was compromised in the absence of Eda. The downstream effects of the Eda pathway are likely to be mediated by transcription factor nuclear factor-B (NF-B), but the transcriptional targets of Edar have remained unknown. Using a quantitative approach, we show in cultured embryonic skin that Eda induced the expression of two Bmp inhibitors, Ccn2/Ctgf (CCN family protein 2/connective tissue growth factor) and follistatin. Moreover, our data indicate that Shh is a likely transcriptional target of Edar, but, unlike noggin, recombinant Shh was unable to rescue primary hair placode formation in Eda-deficient skin explants.

Key words: Ccn2, Ectodermal dysplasia, Lateral inhibition, NF-B, Tabby, Mouse

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				G. D. Richardson, H. Bazzi, K. A. Fantauzzo, J. M. Waters, H. Crawford, P. Hynd, A. M. Christiano, and C. A. B. Jahoda KGF and EGF signalling block hair follicle induction and promote interfollicular epidermal fate in developing mouse skin Development, July 1, 2009; 136(13): 2153 - 2164. [Abstract] [Full Text] [PDF]

				M. Kunisada, C.-Y. Cui, Y. Piao, M. S.H. Ko, and D. Schlessinger Requirement for Shh and Fox family genes at different stages in sweat gland development Hum. Mol. Genet., May 15, 2009; 18(10): 1769 - 1778. [Abstract] [Full Text] [PDF]

				F. Clauss, M.-C. Maniere, F. Obry, E. Waltmann, S. Hadj-Rabia, C. Bodemer, Y. Alembik, H. Lesot, and M. Schmittbuhl Dento-Craniofacial Phenotypes and underlying Molecular Mechanisms in Hypohidrotic Ectodermal Dysplasia (HED): a Review Journal of Dental Research, December 1, 2008; 87(12): 1089 - 1099. [Abstract] [Full Text] [PDF]

				E. Fuchs and J.A. Nowak Building Epithelial Tissues from Skin Stem Cells Cold Spring Harb Symp Quant Biol, November 6, 2008; (2008) sqb.2008.73.032v1. [Abstract] [PDF]

				J. Pispa, M. Pummila, P. A. Barker, I. Thesleff, and M. L. Mikkola Edar and Troy signalling pathways act redundantly to regulate initiation of hair follicle development Hum. Mol. Genet., November 1, 2008; 17(21): 3380 - 3391. [Abstract] [Full Text] [PDF]

				J. Hwang, T. Mehrani, S. E. Millar, and M. I. Morasso Dlx3 is a crucial regulator of hair follicle differentiation and cycling Development, September 15, 2008; 135(18): 3149 - 3159. [Abstract] [Full Text] [PDF]

				F. Michon, L. Forest, E. Collomb, J. Demongeot, and D. Dhouailly BMP2 and BMP7 play antagonistic roles in feather induction Development, August 15, 2008; 135(16): 2797 - 2805. [Abstract] [Full Text] [PDF]

				K. Narhi, E. Jarvinen, W. Birchmeier, M. M. Taketo, M. L. Mikkola, and I. Thesleff Sustained epithelial {beta}-catenin activity induces precocious hair development but disrupts hair follicle down-growth and hair shaft formation Development, March 15, 2008; 135(6): 1019 - 1028. [Abstract] [Full Text] [PDF]

				E. Fuchs Skin stem cells: rising to the surface J. Cell Biol., January 28, 2008; 180(2): 273 - 284. [Abstract] [Full Text] [PDF]

				K. Kobielak, N. Stokes, J. de la Cruz, L. Polak, and E. Fuchs Loss of a quiescent niche but not follicle stem cells in the absence of bone morphogenetic protein signaling PNAS, June 12, 2007; 104(24): 10063 - 10068. [Abstract] [Full Text] [PDF]