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First published online 15 February 2006
doi: 10.1242/dev.02278

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: dev.02278v1 dev.02278v2 133/6/1045    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development 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 Schmidt-Ullrich, R. Articles by Scheidereit, C. Search for Related Content PubMed PubMed Citation Articles by Schmidt-Ullrich, R. Articles by Scheidereit, C.

NF-B transmits Eda A1/EdaR signalling to activate Shh and cyclin D1 expression, and controls post-initiation hair placode down growth

¹ Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13092 Berlin, Germany.
² Medical Biosciences, School of Life Sciences, University of Bradford, Bradford BD7 1DP, UK.
³ Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
⁴ Department of Dermatology, University Hospital Schleswig Holstein, Campus Lübeck, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.

^* Author for correspondence (e-mail: rschmidt{at}mdc-berlin.de)

Accepted 14 December 2005

A novel function of NF-B in the development of most ectodermal appendages, including two types of murine pelage hair follicles, was detected in a mouse model with suppressed NF-B activity (c^IBN). However, the developmental processes regulated by NF-B in hair follicles has remained unknown. Furthermore, the similarity between the phenotypes of c^IBAN mice and mice deficient in Eda A1 (tabby) or its receptor EdaR (downless) raised the issue of whether in vivo NF-B regulates or is regulated by these novel TNF family members. We now demonstrate that epidermal NF-B activity is first observed in placodes of primary guard hair follicles at day E14.5, and that in vivo NF-B signalling is activated downstream of Eda A1 and EdaR. Importantly, ectopic signals which activate NF-B can also stimulate guard hair placode formation, suggesting a crucial role for NF-B in placode development. In downless and c^IBN mice, placodes start to develop, but rapidly abort in the absence of EdaR/NF-B signalling. We show that NF-B activation is essential for induction of Shh and cyclin D1 expression and subsequent placode down growth. However, cyclin D1 induction appears to be indirectly regulated by NF-B, probably via Shh and Wnt. The strongly decreased number of hair follicles observed in c^IBN mice compared with tabby mice, indicates that additional signals, such as TROY, must regulate NF-B activity in specific hair follicle subtypes.

Key words: Hair follicle, NF-B, Eda A1, EdaR, TNF, Skin, Cyclin D1, Shh, TROY (Tnfrsf19), Mouse

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