アクティブボード・２００８年１２月
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研究発表を行った学会；
・第41回 日本発生生物学会大会.
　２００８年５月２８日～３０日(徳島)

タイトル；Embryonic hair follicle fate change by augmented beta-catenin through Shh and Bmp signaling.
　
発表者；　鈴木　堅太郎　氏
　　　（熊本大学　生命資源研究・支援センター　技術開発分野）
Abstract；
　beta-catenin signaling is one of the key factors regulating the fate of hair follicles (HFs). To elucidate the regulatory mechanism of embryonic HF fate determination during epidermal development/differentiation, we analyzed conditional mutant mice with keratinocytes expressing constitutively active beta-catenin (K5-Cre Catnb(ex3)fl/+). The mutant mice developed scaly skin with a thickened epidermis and showed impaired epidermal stratification. The hair shaft keratins were broadly expressed in the epidermis but there was no expression of the terminal differentiation markers K1 or Loricrin. The hair placode markers (Bmp2 and Shh) and follicular dermal condensate markers (Noggin, Patched1 and PDGFRα) were expressed throughout the epidermis and the upper dermis, respectively. These results indicate the embryonic epidermal keratinocytes have switched extensively to the HF fate. A series of genetic studies demonstrated that the epidermal switching to HF fate was suppressed by introducing the conditional mutations of K5-Cre Catnb(ex3)fl/+Shhfl/- (with additional mutation of Shh signaling) or K5-Cre Catnb(ex3)fl/+BmprIAfl/fl (with additional mutation of Bmp signaling). These results demonstrate that Wnt/beta-catenin signaling relayed through Shh and Bmp signals is the principal regulatory mechanism underlying the HF cell fate change. Assessment of the Bmp2 promoter activities suggested a putative regulation by beta-catenin signaling relayed by Shh signaling toward Bmp2. We also found that Shh protein expression was increased and expanded in the epidermis of K5-Cre Catnb(ex3)fl/+BmprIAfl/fl mice. These results indicate the presence of growth factor signal cross-talk involving beta-catenin signaling which regulates the HF fate