近日，英国剑桥大学Magdalena Zernicka-Goetz及其研究团队揭示了调控小鼠胚胎极化的发育时钟。2020年12月11日出版的《科学》杂志发表了这项成果。

研究人员发现，胚胎极化时钟反映了合子基因组激活的开始，并确定了触发极化所需的三个因素。在存在激活的Ras同源家族成员A（RhoA）的情况下，将转录因子AP-2γ（Tfap2c）和TEA域转录因子4（Tead4）的表达时间提前能够诱导早熟极化以及随后的细胞命运分化和形态发生。Tfap2c和Tead4诱导肌动蛋白调节因子的表达，该蛋白控制膜上顶端蛋白的募集，而RhoA调节其横向移动性，从而允许顶端结构域的出现。因此，Tfap2c、Tead4和RhoA是小鼠中极化和细胞命运分化的调节因子。

据了解，胚胎极化对于小鼠发育至关重要。但是，调节时钟及其激活的分子触发因子均未知。 

附：英文原文

Title: Developmental clock and mechanism of de novo polarization of the mouse embryo

Author: Meng Zhu, Jake Cornwall-Scoones, Peizhe Wang, Charlotte E. Handford, Jie Na, Matt Thomson, Magdalena Zernicka-Goetz

Issue&Volume: 2020/12/11

Abstract: 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.

DOI: 10.1126/science.abd2703

Source: https://science.sciencemag.org/content/370/6522/eabd2703