Tissue renewal is an ongoing process in the epithelium of the skin. We have begun to examine the genetic mechanisms that control stem/progenitor cell activation in the postnatal epidermis. The conserved Hippo pathway regulates stem cell turn over in arthropods through to vertebrates. We show here that its downstream effector Yes-associated protein (YAP) is active in the stem/progenitor cells of the postnatal epidermis. Overexpression of a C-terminally truncated YAP protein mutant in the basal epidermis of transgenic mice caused dramatic expansion of epidermal stem/progenitor cell populations. Our data suggest that the C-terminus of YAP controls the balance between stem/progenitor cell proliferation and differentiation in the postnatal interfollicular epidermis. We conclude that YAP functions as a molecular switch of stem/progenitor cell activation in the epidermis. Moreover, our results highlight YAP as a possible therapeutic target for diseases such as skin cancer, psoriasis and epidermolysis bullosa.

(Accepted for publication in Journal of Investigative Dermatology)