Development requires coordinated interactions between the epiblast, which generates the embryo proper; the trophectoderm, which generates the placenta; and the hypoblast, which forms both the anterior signalling centre and the yolk sac. These interactions remain poorly understood in human embryogenesis because mechanistic studies have only recently become possible. Here we examine signalling interactions post-implantation using human embryos and stem cell models of the epiblast and hypoblast. We find anterior hypoblast specification is NODAL dependent, as in the mouse. However, while BMP inhibits anterior signalling centre specification in the mouse, it is essential for its maintenance in human. We also find contrasting requirements for BMP in the naive pre-implantation epiblast of mouse and human embryos. Finally, we show that NOTCH signalling is important for human epiblast survival. Our findings of conserved and species-specific factors that drive these early stages of embryonic development highlight the strengths of comparative species studies.

发育需要外胚层之间的协调相互作用，从而产生胚胎本身。滋养外胚层，产生胎盘；和下胚层，形成前信号中心和卵黄囊。由于机制研究最近才成为可能，因此人类胚胎发生中的这些相互作用仍然知之甚少。在这里，我们使用人类胚胎以及外胚层和下胚层的干细胞模型检查植入后的信号相互作用。我们发现前下胚层的规格是 NODAL 依赖性的，就像在小鼠中一样。然而，虽然 BMP 抑制小鼠前部信号中心的规范，但它对于人类的维持至关重要。我们还发现小鼠和人类胚胎的幼稚植入前外胚层对 BMP 的需求存在差异。最后，我们证明 NOTCH 信号传导对于人类外胚层的存活很重要。我们对驱动胚胎发育早期阶段的保守和物种特异性因素的发现凸显了比较物种研究的优势。