040 Epithelial-mesenchymal interaction and hair cycling

Jiro Kishimoto, Tsutomu Soma, Toshihiko Hibino, Bruce Morgan*, Robert Burgeson*. Shiseido Life Science Research Center, MGH/Harvard Cutaneous Biology Research Center*

Hair dermal papilla cells are specialized mesenchymal cells, which send reciprocal signals to hair follicular stem cells to maintain hair elongation and cyclic regeneration. Several epithelial derived signaling molecules such as Shh and Wnt –beta catenin have shown their essential roles for anagen induction in transgenic mouse model but direction of signal and actual targets in dermal papilla cells are to be elucidated. Versican is a large chondroitin sulfate proteoglycan and in situ hybridization results showed anagen dermal papilla (DP) specific versican expression in mice as well as previous immunohistochemical study. Localization of versican in human hair follicle by core-protein specific monoclonal antibody also demonstrated anagen dependent staining in human DP similar to mice, suggesting a common role of versican across the species. We have generated lacZ reporter transgenic mouse with versican promoter and successfully obtained DP specific promoter activation in vivo during development and postnatal hair cycling. Pelage dermal papilla cells are isolated from versican transgenic line with GFP reporter by FACS. Affymetrix gene chip analysis using isolated DP cells indicates abundant gene expression characteristic to DP cells previously reported such as collagen I and III. These isolated DP cells have proved to possess hair inductive activity by hair reconstitution grafting assay, however, without stimulation from epithelial cells they lose this inductivity during passages in culture. This inductivity was able to maintain by feeding biological active Wnt protein in culture, indicating Wnt signaling from follicular epithelium toward DP has essential role for hair elongation. Current effort is focused to reactivate cultured inactive DP cells including by simultaneous stimulation of multiple signaling molecules and forced expression of versican itself.