The Wellcome Trust/Cancer Research UK Gurdon Institute, the Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Nat Commun. 2013;4:2251. doi: 10.1038/ncomms3251.
Cell identity is specified in the early mammalian embryo by the generation of precursors for two cell lineages: the pluripotent inner cell mass and differentiating trophectoderm. Here we identify Angiomotin as a key regulator of this process. We show that the loss of Angiomotin, together with Angiomotin-like 2, leads to differentiation of inner cell mass cells and compromised peri-implantation development. We show that Angiomotin regulates localization of Yap, and Yap-binding motifs are required for full activity of Angiomotin. Importantly, we also show that Angiomotin function can compensate for the absence of Lats1/2 kinases, indicating the ability of Angiomotin to bypass the classical Hippo pathway for Yap regulation. In polarized outside cells, Angiomotin localizes apically, pointing to the importance of cell polarity in regulating Yap to promote differentiation. We propose that both Hippo pathway-dependent and Hippo pathway-independent mechanisms regulate Yap localization to set apart pluripotent and differentiated lineages in the pre-implantation mouse embryo.
多能的内细胞团和分化的滋养外胚层。在这里，我们鉴定出 Angiomotin 是这一过程的关键调节因子。我们表明，Angiomotin 与 Angiomotin-like 2 的缺失导致内细胞团细胞的分化和着床前发育受损。我们表明 Angiomotin 调节 Yap 的定位，并且 Yap 结合基序是 Angiomotin 完全活性所必需的。重要的是，我们还表明 Angiomotin 功能可以补偿 Lats1/2 激酶的缺失，表明 Angiomotin 能够绕过 Yap 调节的经典 Hippo 通路。在极化的外部细胞中，Angiomotin 定位于顶端，这表明细胞极性在调节 yap 以促进分化方面的重要性。我们提出，Hippo 通路依赖性和 Hippo 通路非依赖性机制调节 yap 的定位，以区分植入前小鼠胚胎中的多能和分化谱系。
