cell depletion through epidermal deletion of Rac1

Mammalian epidermis is maintained by self-renewal of stem cells, but the underlying mechanisms are unknown. Deletion of Rac1, a Rho guanosine tri-phosphatase, in adult mouse epidermis stimulated stem cells to divide and undergo terminal differentiation, leading to failure to maintain the interfollic-ular epidermis, hair follicles, and sebaceous glands. Rac1 exerts its effects in the epidermis by negatively regulating c-Myc through p21-activated kinase 2 (PAK2) phosphorylation. We conclude that a pleiotropic regulator of cell adhesion and the cytoskeleton plays a critical role in controlling exit from the stem cell niche and propose that Rac and Myc represent a global stem cell regulatory axis. Mammalian epidermis is maintained by prolif-eration of stem cells and differentiation of their progeny along the lineages of the interfollicu-lar epidermis (IFE), sebaceous gland (SG), and hair follicle (HF) (1). Although studies of cul