Cdc42 controls progenitor cell differentiation and β-catenin turnover in skin

Differentiation of skin stem cells into hair follicles (HFs) requires the inhibition of β-catenin degradation, which is controlled by a complex containing axin and the protein kinase GSK3β. Using conditional gene targeting in mice, we show now that the small GTPase Cdc42 is crucial for differentiation of skin progenitor cells into HF lineage and that it regulates the turnover of β-catenin. In the absence of Cdc42, degradation of β-catenin was increased corresponding to a decreased phosphorylation of GSK3β at Ser 9 and an increased phosphorylation of axin, which is known to be required for binding of β-catenin to the degradation machinery. Cdc42-mediated regulation of β-catenin turnover was completely dependent on PKCζ, which associated with Cdc42, Par6, and Par3. These data suggest that Cdc42 regulation of β-catenin turnover is important for terminal differentiation of HF progenitor cells in vivo. © 2006 by Cold Spring Harbor Laboratory Press.