The role of Smads in skin development.

Smads are a group of signaling mediators and antagonists of the transforming growth factor-beta (TGF-beta) superfamily, responding but not limited to signaling from TGF-beta, Activin, and bone morphogenetic proteins (BMPs). As all of these three signaling pathways play important roles in skin development, we have been actively pursuing studies assessing the role of Smads in skin development. Our studies revealed that Smad-4 affects hair follicle differentiation primarily by mediating BMP signaling. Smad-7 significantly affects hair follicle development and differentiation by blocking the TGFbeta/Activin/BMP pathway and by inhibiting WNT/beta-catenin signaling via ubiquitin-mediated beta-catenin degradation. In contrast, other Smads may have redundant or dispensable functions in skin development. Here, we review the work that shows the emergence of Smad functions in skin development via traditional and novel signaling pathways.