Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Division of Biology and Biological Engineering, California Institute of Technology (Caltech), Pasadena, CA 91125, USA.
Science. 2020 Dec 11;370(6522). doi: 10.1126/science.abd2703.
Embryo polarization is critical for mouse development; however, neither the regulatory clock nor the molecular trigger that it activates is known. Here, we show that the embryo polarization clock reflects the onset of zygotic genome activation, and we identify three factors required to trigger polarization. Advancing the timing of transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4) expression in the presence of activated Ras homolog family member A (RhoA) induces precocious polarization as well as subsequent cell fate specification and morphogenesis. Tfap2c and Tead4 induce expression of actin regulators that control the recruitment of apical proteins on the membrane, whereas RhoA regulates their lateral mobility, allowing the emergence of the apical domain. Thus, Tfap2c, Tead4, and RhoA are regulators for the onset of polarization and cell fate segregation in the mouse.
胚胎极化对于小鼠发育至关重要；然而，目前尚不清楚调节时钟或它激活的分子触发因素是什么。在这里，我们表明胚胎极化时钟反映了合子基因组激活的开始，并且我们确定了触发极化所需的三个因素。在激活的 Ras 同源家族成员 A（RhoA）存在的情况下，提前表达转录因子 AP-2 伽马（Tfap2c）和 TEA 结构域转录因子 4（Tead4）会诱导过早极化以及随后的细胞命运特化和形态发生。Tfap2c 和 Tead4 诱导控制膜上顶端蛋白募集的肌动蛋白调节剂的表达，而 RhoA 调节它们的侧向流动性，从而出现顶端区域。因此，Tfap2c、Tead4 和 RhoA 是小鼠极化和细胞命运分离开始的调节剂。
