P#31  Epidermal-dermal interaction required for inducing the dermal condensation during hair follicle development

Inamatsu1, 2, 3, Aya Makabe3, Koh-ei Toyoshima2 and Katsutoshi Yoshizato1, 3. 1Hiroshima Tissue Regeneration Project, Hiroshima Prefecture Collaboration of Regional Entities for the Advancement of Technological Excellence, JST, Hiroshima, Japan; 2Institute of Immunology Co., Ltd., Tokyo, Japan; 3Dept of Biol. Sci., Grad. School of Sci., Hiroshima Univ., Hiroshima, Japan

We studied the epidermal-dermal interaction involved in embryonic development of rat hair follicles. Pelage hair germs started to form at 16 days after coitus (E16) in Fisher rats. We transplanted skins separated from embryos at varied stages of hair development onto the back of nude mice. No hairs were formed in E14 skin transplants. Hairs were induced in the transplants prepared from the embryonic skin at any stage after E15, although the induction rate depended on the developmental stage of skin, 100% induction being observed at stages later than E17. We asked whether the induction of hair germ requires the interaction between the embryonic epidermis and the underlying mesenchyme. To address this question we separated epidermis and dermis from the skin at various embryonic stages and prepared "recombinant skin" by combining the epidermis at a developmental stage with the dermis at another stage. The recombinant skin was transplanted onto the back of nude mice to observe hair development in the transplants. We found that hairs were formed in transplants composed of E17-epidermis and E14- or E17-mesenchyme, but not formed in transplants composed of E14-epidermis and E14- or E17-mesenchyme. Thus, we hypothesized that E17-epidermis could induce dermal condensation in E14-dermis that had not formed dermal condensation in vivo. To prove this hypothesis, we prepared the recombinant embryonic skin using green fluorescence protein (GFP)-transgenic Wistar rats (GFP-TgRs). The transgene was driven by b-actin promoter. The recombinant skin was transplanted onto the back of nude mice as above. Transplants composed of E17-epidermis of GFP-TgRs and E13-dermis of wild rats produced hair follicles that contained GFP-positive hair follicle epidermal cells and GFP-negative dermal papilla cells. Transplants composed of E17-epidermis of wild rats and E13-dermis of GFP-TgRs produced hair follicles that contained GFP-negative hair follicle epidermal cells and GFP-positive dermal papilla cells. The present study showed that the epidermal-dermal interactions play critical roles in inducing hair follicles in embryonic skin. One of such interactions was seen in the dermal condensation that leads to the formation of dermal papilla. Embryonic epidermis is concluded to exert a leading action on the embryonic immature dermis to induce the dermal condensation. This critical event takes place around at E15.