SONIC HEDGEHOG SIGNALING IS ESSENTIAL FOR HAIR DEVELOPMENT

Background: The skin is responsible for forming a variety of epidermal structures that differ amongst vertebrates, In each case the specific structure (for example scale, feather or hair) arises from an epiderm al placode as a result of epithelial-mesenchymal interactions with the underlying dermal mesenchyme, Expression of members of the Wnt, Hedge hog and bone morphogenetic protein families (Wnt10b, Sonic hedgehog (S hh) and Bmp2/Bmp4 respectively) in the epidermis correlates with the i nitiation of hair follicle formation, Further, their expression contin ues into either the epidermally derived hair matrix which forms the ha ir itself, or the dermal papilla which is responsible for induction of the hair matrix. To address the role of Shh in the hair follicle, we have examined Shh null mutant mice. Results: We found that follicle de velopment in the Shh mutant embryo arrested after the initial epiderma l-dermal interactions that lead to the formation of a dermal papilla a nlage and ingrowth of the epidermis, Wnt10b, Bmp2 and Bmp4 continued t o be expressed at this time, however. When grafted to nude mice (which lack T cells), Shh mutant skin gave rise to large abnormal follicles containing a small dermal papilla, Although these follicles showed hig h rates of proliferation and some differentiation of hair matrix cells into hair-shaft-like material, no hair was formed. Conclusions: Shh s ignaling is not required for initialing hair follicle development. Shh signaling is essential, however, for controlling ingrowth and morphog enesis of the hair follicle.