诺金
生物
毛囊
细胞生物学
祖细胞
Wnt信号通路
内根鞘
WNT5A型
祖细胞
骨形态发生蛋白
基因
信号转导
干细胞
外根鞘
遗传学
作者
Krzysztof Kobielak,H. Amalia Pasolli,Laura C. Alonso,Lisa Polak,Elaine Fuchs
标识
DOI:10.1083/jcb.200309042
摘要
Using conditional gene targeting in mice, we show that BMP receptor IA is essential for the differentiation of progenitor cells of the inner root sheath and hair shaft. Without BMPRIA activation, GATA-3 is down-regulated and its regulated control of IRS differentiation is compromised. In contrast, Lef1 is up-regulated, but its regulated control of hair differentiation is still blocked, and BMPRIA-null follicles fail to activate Lef1/β-catenin–regulated genes, including keratin genes. Wnt-mediated transcriptional activation can be restored by transfecting BMPRIA-null keratinocytes with a constitutively activated β-catenin. This places the block downstream from Lef1 expression but upstream from β-catenin stabilization. Because mice lacking the BMP inhibitor Noggin fail to express Lef1, our findings support a model, whereby a sequential inhibition and then activation of BMPRIA is necessary to define a band of hair progenitor cells, which possess enough Lef1 and stabilized β-catenin to activate the hair specific keratin genes and generate the hair shaft.
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