PDF(Pubmed)
Abstract：
The mouse and human embryo gradually loses totipotency before diversifying into the inner cell mass (ICM, future organism) and trophectoderm (TE, future placenta). The transcription factors TFAP2C and TEAD4 with activated RHOA accelerate embryo polarization. Here we show that these factors also accelerate the loss of totipotency. TFAP2C and TEAD4 paradoxically promote and inhibit Hippo signaling before lineage diversification: they drive expression of multiple Hippo regulators while also promoting apical domain formation, which inactivates Hippo. Each factor activates TE specifiers in bipotent cells, while TFAP2C also activates specifiers of the ICM fate. Asymmetric segregation of the apical domain reconciles the opposing regulation of Hippo signaling into Hippo OFF and the TE fate, or Hippo ON and the ICM fate. We propose that the bistable switch established by TFAP2C and TEAD4 is exploited to trigger robust lineage diversification in the developing embryo.
摘要：
小鼠和人类胚胎在多样化进入内细胞团之前逐渐失去全能性(ICM，未来生物)和滋养外胚层(TE，未来胎盘)。具有激活的RHOA的转录因子TFAP2C和TEAD4加速胚胎极化。在这里，我们表明这些因素也加速了全能性的丧失。TFAP2C和TEAD4在谱系多样化之前矛盾地促进和抑制Hippo信号：它们驱动多种Hippo调节因子的表达，同时还促进顶端结构域的形成，使河马失活。每个因子激活双能细胞中的TE说明符，而TFAP2C也激活ICM命运的说明符。顶端域的不对称分离协调了Hippo信号传导到HippoOFF和TE命运的相反调节，或河马和ICM的命运。我们建议利用TFAP2C和TEAD4建立的双稳态开关来触发发育中胚胎的强大谱系多样化。
