Gab1 and Mapk Signaling Are Essential in the Hair Cycle and Hair Follicle Stem Cell Quiescence
Gab1 and Mapk Signaling Are Essential in the Hair Cycle and Hair Follicle Stem Cell Quiescence
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DOI：
10.1016/j.celrep.2015.09.015
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发表时间：
2015-10-20
期刊：
影响因子：
8.8
通讯作者：
Birchmeier, Walter
中科院分区：
文献类型：
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作者：
Oeztuerk, Oezlem Akilli;Pakula, Hubert;Birchmeier, Walter
Gab 1是一种作用于受体酪氨酸激酶下游的支架蛋白。在这里，我们产生了条件性Gab 1突变小鼠（通过K14-和Krox 20-cre），并表明Gab 1介导了控制毛发周期和毛囊干细胞自我更新的关键信号。值得注意的是，突变的毛囊不会进入退化期，即头发周期的破坏性阶段。相反，毛囊干细胞失去了静止状态，变得疲惫不堪，因此在凸起中没有干细胞龛。此外，通过表达功能获得性Mek 1（DD）等位基因（通过Krox 20-cre）有条件地持续激活Mapk信号传导，可以挽救毛发周期缺陷并恢复干细胞的静止。因此，我们的数据表明Gab 1受体酪氨酸激酶下游和Shp 2和Mapk上游的头发周期和毛囊干细胞的自我更新的调节中的重要作用。
Gab1 is a scaffold protein that acts downstream of receptor tyrosine kinases. Here, we produced conditional Gab1 mutant mice (by K14- and Krox20-cre) and show that Gab1 mediates crucial signals in the control of both the hair cycle and the self-renewal of hair follicle stem cells. Remarkably, mutant hair follicles do not enter catagen, the destructive phase of the hair cycle. Instead, hair follicle stem cells lose quiescence and become exhausted, and thus no stem cell niches are established in the bulges. Moreover, conditional sustained activation of Mapk signaling by expression of a gain-of-function Mek1(DD) allele (by Krox20-cre) rescues hair cycle deficits and restores quiescence of the stem cells. Our data thus demonstrate an essential role of Gab1 downstream of receptor tyrosine kinases and upstream of Shp2 and Mapk in the regulation of the hair cycle and the self-renewal of hair follicle stem cells.