B5.4 SIGNALING FROM DERMAL PAPILLA CELLS

Jiro Kishimoto, Ritsuko Ehama, Tsutomu Soma, Ritsuro Ideta, Ki-ichiro Yamo

Shiseido Research Center, Yokohama, Japan

Reciprocal epithelial-mesenchymal interaction (EMI) between follicular stem cells and dermal papilla cells are central roles in hair follicle development and hair cycling.

Compared with rapid progress of follicular stem cell research,　detailed characterization and signals from mesenchymal papilla are virtually unknown. However, accumulating evidence emphasizes the functional importance of extracellular matrix and proteoglycans that occupies between these two compartments as either target molecules or modulators for epithelial signaling molecules. Among them, versican, a large chondroitin sulfate proteoglycan, expresses specifically in human dermal papilla at anagen onset, and remain its immunoreactivity in the bulge region of hair follicles, suggesting its functional significance in EMI. The importance of this molecule has been recently reported by Nakamura et al. that up-regulation of versican in murine embryonic stem cells could lead them to differentiate into the hair inductive mesenchyme. Enrichment of dermal papilla cells from versican promoter?driven reporter transgenic mice and subsequent cellular grafting with newborn murine epidermal cells revealed versican-expressing primary dermal papilla cells have highly inductive property to reconstitute the hair follicles. Not only arografting, but also hair generation by xenografting with rat and human-origin epidermal keratinocytes, indicates these murine mesenchymal papillae possess powerful inductive ability in EMI across species. DNA microarray analysis between inductive and non-inductive cultured murine papilla cells showed multiple candidate genes for the maintenance of this inductivity, including growth factors, angiogenetic factors, and cell cycle regulating genes. Beside known molecules, changes of the genes involved in fibrogenesis such as fibromodulin and connective tissue growth factor, imply the precise control of connective tissue formation may have an additional role in EMI during hair follicle formation. Further progress in EMI research and characterization of human dermal papilla cells could give us how to proliferate human follicular papillae in culture while maintaining their inductive property in order to achieve successful human hair follicle generation.