β-catenin controls hair follicle morphogenesis and stem cell differentiation in the skin

β-catenin controls hair follicle morphogenesis and stem cell differentiation in the skin
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DOI:
10.1016/s0092-8674(01)00336-1
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发表时间:
2001-05-18
期刊:
影响因子:
64.5
通讯作者:
Birchmeier, W
Birchmeier, W
中科院分区:
生物学1区
文献类型:
--
作者:
Huelsken, J;Vogel, R;Birchmeier, W

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β-连环蛋白是Wnt/wingless信号传导中的必需分子,其控制胚胎发生中的决定性步骤。为了研究β-连环蛋白在皮肤发育中的作用,我们使用Cre/loxP技术在表皮和毛囊中引入该基因的条件突变。当β-连环蛋白在胚胎发育过程中发生突变时,产生毛囊的基板的形成就被阻断了。我们发现β-连环蛋白在遗传上是必需的,在基板形成中,在虎斑/无绒毛的下游和BMP和SHH的上游。如果β-连环蛋白在毛囊形成后被删除,头发在第一个毛发周期后就完全脱落了。进一步的分析表明,β-连环蛋白对于皮肤干细胞的命运决定是必不可少的:在β-连环蛋白不存在的情况下,干细胞倾向于分化成滤泡角质形成细胞,而是采取表皮命运.
beta -Catenin is an essential molecule in Wnt/wingless signaling, which controls decisive steps in embryogenesis. To study the role of beta -catenin in skin development, we introduced a conditional mutation of the gene in the epidermis and hair follicles using Cre/loxP technology. When beta -catenin is mutated during embryogenesis, formation of placodes that generate hair follicles is blocked. We show that beta -catenin is required genetically downstream of tabby/downless and upstream of bmp and shh in placode formation. If beta -catenin is deleted after hair follicles have formed, hair is completely lost after the first hair cycle. Further analysis demonstrates that beta -catenin is essential for fate decisions of skin stem cells: in the absence of beta -catenin, stem cells rail to differentiate into follicular keratinocytes, but instead adopt an epidermal fate.