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Published online on September 29, 2005, 10.1073/pnas.0507609102
PNAS | October 11, 2005 | vol. 102 | no. 41 | 14653-14658


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DEVELOPMENTAL BIOLOGY
Hairless triggers reactivation of hair growth by promoting Wnt signaling

Gerard M. J. Beaudoin, III *, {dagger}, Jeanne M. Sisk *, Pierre A. Coulombe {ddagger}, §, and Catherine C. Thompson *, {dagger}, ¶, ||

*Kennedy Krieger Research Institute and Departments of {dagger}Neuroscience, Molecular Biology and Genetics, {ddagger}Biological Chemistry, and §Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21205

Communicated by Donald D. Brown, Carnegie Institution of Washington, Baltimore, MD, August 31, 2005 (received for review August 9, 2005)

The mammalian hair cycle involves periodic regeneration of a tiny organ, the hair follicle, through a stem-cell-mediated process. The Hairless (Hr) gene encodes a nuclear receptor corepressor (HR) that is essential for hair follicle regeneration, but its role in this process is unknown. Here, we demonstrate that transgenic expression of HR in progenitor keratinocytes rescues follicle regeneration in Hr-/- mice. We show that expression of Wise, a modulator of Wnt signaling, is repressed by HR in these cells, coincident with the timing of follicle regeneration. This work links HR and Wnt function, providing a model in which HR regulates the precise timing of Wnt signaling required for hair follicle regeneration.

corepressor | nuclear receptor | skin

Author contributions: G.M.J.B. and C.C.T. designed research; G.M.J.B. and J.M.S. performed research; G.M.J.B., P.A.C., and C.C.T. analyzed data; G.M.J.B. and C.C.T. wrote the paper; and J.M.S. provided artwork.

Abbreviations: DP, dermal papilla; ORS, outer root sheath; Pn, postnatal day n; Shh, sonic hedgehog.

|| To whom correspondence should be addressed at: Kennedy Krieger Institute, 707 North Broadway, Baltimore, MD 21205. E-mail: thompsonc{at}kennedykrieger.org.

© 2005 by The National Academy of Sciences of the USA


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