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.
