Sustained epithelial β-catenin activity induces precocious hair development but disrupts hair follicle down-growth and hair shaft formation
Sustained epithelial β-catenin activity induces precocious hair development but disrupts hair follicle down-growth and hair shaft formation
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DOI：
10.1242/dev.016550
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发表时间：
2008-03-15
期刊：
影响因子：
4.6
通讯作者：
Thesleff, Irma
中科院分区：
文献类型：
--
作者：
Narhi, Katja;Jarvinen, Elina;Thesleff, Irma
在胚胎和出生后的发育过程中，Wnt/β-连环蛋白信号参与了从基板形成到毛干分化的毛发形态发生的几个阶段。使用转基因的方法，我们进一步研究了β-连环蛋白信号在胚胎毛发发育中的作用。即使在缺乏Eda/Edar信号传导的情况下，β-连环蛋白的强制上皮稳定化也导致毛囊的早熟和过度诱导，Eda/Edar信号传导是初级毛基板形成所必需的途径。此外，基板的间距和尺寸是随机的。令人惊讶的是，毛囊的向下生长受到抑制，毛干的产生严重受损。基因和报告基因表达分析显示，在整个皮肤中，间充质Wnt活性升高，以及BMP信号传导增加，伴随着Sostdc 1（Wise，ectodin）表达的上调。我们的数据表明，BMP是Wnt/β-连环蛋白的下游，它们的相互作用可能是通过反应扩散机制建立毛囊正确模式的关键组成部分。
During embryonic and postnatal development, Wnt/beta-catenin signaling is involved in several stages of hair morphogenesis from placode formation to hair shaft differentiation. Using a transgenic approach, we have investigated further the role of beta-catenin signaling in embryonic hair development. Forced epithelial stabilization of beta-catenin resulted in precocious and excessive induction of hair follicles even in the absence of Eda/Edar signaling, a pathway essential for primary hair placode formation. In addition, the spacing and size of the placodes was randomized. Surprisingly, the down-growth of follicles was suppressed and hair shaft production was severely impaired. Gene and reporter expression analyses revealed elevated mesenchymal Wnt activity, as well as increased BMP signaling, throughout the skin that was accompanied by upregulation of Sostdc1 (Wise, ectodin) expression. Our data suggest that BMPs are downstream of Wnt/beta-catenin and that their interplay may be a critical component in establishing correct patterning of hair follicles through the reaction-diffusion mechanism.