March 2017 - Vol 137 No 3

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In a series of elegant experiments, Akladios and colleagues establish that YAP, a critical regulator of stem and progenitor cell proliferation, does so by signaling through b-catenin. They first show that YAP co-localizes in keratinocyte nuclei with b-catenin during cell proliferation, that inactivating YAP in these cells reduces b-catenin activation and cell growth, and that transfecting mice with a mutant hyperactive form of YAP termed YAP2-5SA-DC increases b-catenin activity and causes epidermal hyperplasia that is reversed by loss of b-catenin. As shown in the cover image, using TOPFLASH mice transgenic for a bioluminescence system driven by activated b-catenin, the authors also show that YAP2-5SA-DC has the same effect in vivo. The quantifiable radiance is far higher in YAP2-5SA-DC/TOPFLASH mice than in single transgenic control TOPFLASH mice throughout the hair cycle (telogen in upper panel and anagen in lower panel), but strikingly so in anagen phase, consistent with the known increase in WNT-b-catenin signaling at this time of rapid cell proliferation. For details, see the article on page 716.