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First published online 6 February 2008
doi: 10.1242/dev.016550

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Sustained epithelial β-catenin activity induces precocious hair development but disrupts hair follicle down-growth and hair shaft formation

Katja Närhi¹, Elina Järvinen¹, Walter Birchmeier², Makoto M. Taketo³, Marja L. Mikkola^1,* and Irma Thesleff^1,*,

¹ Developmental Biology Program, Institute of Biotechnology, Viikki Biocenter, PO Box 56, University of Helsinki, FIN-00014, Helsinki, Finland.
² Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13092 Berlin, Germany.
³ Department of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.

Author for correspondence (e-mail: irma.thesleff{at}helsinki.fi)

Accepted 7 January 2008

During embryonic and postnatal development, Wnt/β-catenin signaling is involved in several stages of hair morphogenesis from placode formation to hair shaft differentiation. Using a transgenic approach, we have investigated further the role of β-catenin signaling in embryonic hair development. Forced epithelial stabilization of β-catenin resulted in precocious and excessive induction of hair follicles even in the absence of Eda/Edar signaling, a pathway essential for primary hair placode formation. In addition, the spacing and size of the placodes was randomized. Surprisingly, the down-growth of follicles was suppressed and hair shaft production was severely impaired. Gene and reporter expression analyses revealed elevated mesenchymal Wnt activity, as well as increased BMP signaling, throughout the skin that was accompanied by upregulation of Sostdc1 (Wise, ectodin) expression. Our data suggest that BMPs are downstream of Wnt/β-catenin and that their interplay may be a critical component in establishing correct patterning of hair follicles through the reaction-diffusion mechanism.

Key words: Hair, Placode, Follicle, β-catenin, BMP, Lateral inhibition, Mouse

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