Hairless triggers reactivation of hair growth by promoting Wnt signaling

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 Writ signaling, is repressed by HR in these cells, coincident with the timing of follicle regeneration. This work links HR and Writ function, providing a model in which HR regulates the precise timing of Wnt signaling required for hair follicle regeneration.