Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
Curr Top Dev Biol. 2018;128:11-35. doi: 10.1016/bs.ctdb.2017.10.008. Epub 2017 Nov 22.
During the first few days in the mouse preimplantation embryo, two types of cells, polar and apolar cells are generated from spherical totipotent blastomeres. Sequential morphogenetic events, polarization, compaction, and asymmetric division, are essential for the generation of the first distinct cell populations, polar and apolar cells, which establish the outer/inner configuration within the embryo. This leads to position-dependent activation of the Hippo signaling pathway and lineage-specific gene expression to form the trophectoderm and inner cell mass in a blastocyst. It is still unknown how each morphogenetic event is initiated and how it influences subsequent events. In this chapter, we briefly review the two classic models of mouse preimplantation development and discuss recent studies providing novel insights into the self-organizing ability of the preimplantation mouse embryo. Advances in live cell imaging and mathematical modeling contribute a greater understanding to lineage specification and cell fate commitment at the single cell level. Differential molecular and mechanistic characteristics created by the presence and absence of the apical domain in polar and apolar cells, respectively, dictate cell allocation, divisional orientation, and differential activation of the Hippo signaling pathway.
在小鼠胚胎植入前的最初几天,从球形全能卵裂球中产生了两种类型的细胞,极性细胞和无极性细胞。连续的形态发生事件,如极化、致密化和不对称分裂,对于产生第一批独特的细胞群体——极性细胞和无极性细胞是至关重要的,这些细胞群体在胚胎内部建立了外/内结构。这导致 Hippo 信号通路的位置依赖性激活和谱系特异性基因表达,从而在胚泡中形成滋养外胚层和内细胞团。目前尚不清楚每个形态发生事件是如何启动的,以及它如何影响后续事件。在这一章中,我们简要回顾了经典的小鼠胚胎植入前发育模型,并讨论了最近的研究,这些研究为小鼠胚胎的自我组织能力提供了新的见解。活细胞成像和数学建模的进展使我们对谱系特化和单细胞水平的细胞命运决定有了更深入的理解。极性细胞和无极性细胞中存在和不存在顶端结构域分别导致了不同的分子和机制特征,这些特征决定了细胞的分配、分裂方向和 Hippo 信号通路的差异激活。