Instructive roles of mesenchymal proteoglycans in hair follicle morphogenesis and maintenance

PROJECT SUMMARY Hair is produced in the hair follicles. Hair follicle formation, cycling, and neogenesis relies on extensive cross- talk between hair follicle keratinocytes and dermal papilla cells. This cross-talk is primarily mediated by molecular signaling pathways. In classic models of molecular signaling, a ligand binds and activates a receptor on the surface of a cell to produce a signal into the cell body. Such signal may influence a cell’s ability to proliferate, differentiate, migrate, contract, and more. Integrins exist on the surface of many cell types. They serve three basic functions: adhesion, scaffolding, and signaling. The functions of integrins in the hair follicles are not fully understood. We obtained evidence supporting a role of integrin in transducing signals from the extracellular matrix into hair follicle keratinocytes to promote its proliferation. The extracellular matrix is made of proteins produced by the dermal papilla cells. One major component of these proteins are proteoglycans. Here, we propose a new form of cross-talk that proteoglycans produced by dermal papilla cells activates integrins on hair matrix keratinocytes to promote hair growth. In this proposal, we will investigate 1) how production of proteoglycans is controlled in dermal papilla cells, 2) the functions of proteoglycans on dermal papilla formation, 3) how proteoglycans control hair follicle formation and regeneration, and finally, 4) whether impairment in proteoglycans production is responsible for hedgehog inhibitor-induced hair loss. Results obtained from this study may provide new insight into the basic biology of hair follicle, and advance our understanding on hair loss.