Essential role for Sonic hedgehog during hair follicle morphogenesis

The hair follicle is a source of epithelial stem cells and site of origin f or several types of skin tumors. Although it is clear that follicles arise by way of a series of inductive tissue interactions, identification of the signaling molecules driving this process remains a major challenge in skin biology. In this study we report an obligatory role for the secreted morpho gen Sonic hedgehog (Shh) during hair follicle development. Hair germs compr ising epidermal placodes and associated dermal condensates were detected in both control and Shh -/- embryos, but progression through subsequent stage s of follicle development was blocked in mutant skin. The expression of Gli 1 and Ptc1 was reduced in Shh -/- dermal condensates and they failed to evo lve into hair follicle papillae, suggesting that the adjacent mesenchyme is a critical target for placode-derived Shh. Despite the profound inhibition of hair follicle morphogenesis, late-stage follicle differentiation marker s were detected in Shh -/- skin grafts, as well as cultured vibrissa explan ts treated with cyclopamine to block Shh signaling. Our findings reveal an essential role for Shh during hair follicle morphogenesis, where it is requ ired for normal advancement beyond the hair germ stage of development. (C) 1999 Academic Press.