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Title Embryonic hair follicle fate change by augmented Beta-catenin through Shh and Bmp signaling
Posted by Mylah Tabelin
Authors Kentaro Suzuki, Yuji Yamaguchi, Mylah Villacorte, Kenichiro Mihara, Masashi Akiyama, Hiroshi Shimizu, Makoto M Taketo, Naomi Nakagata, Tadasuke Tsukiyama, Terry P Yamaguchi, Walter Birchmeier, Shigeaki Kato, Gen Yamada
Publication date 2009/2/1
Journal Development
Volume 136
Issue 3
Pages 367-372
Publisher The Company of Biologists
Abstract β-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 activeβ -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 and loricrin. Hair placode markers (Bmp2 and Shh) and follicular dermal condensate markers (noggin, patched 1 and Pdgfra) were expressed throughout the epidermis and the upper dermis, respectively. These results indicate that 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 mutation 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/β-catenin signaling relayed through Shh and Bmp signals is the principal regulatory mechanism underlying the HF cell fate change. Assessment of Bmp2 promoter activities suggested a putative regulation by β-catenin signaling relayed by Shh signaling towards 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 β-catenin signaling, which regulates the HF fate.
Index terms / Keywords Skin; Hair follicle (HF); Wntβ-catenin; Bmp
DOI doi: 10.1242/dev.021295