早期胚胎极性建立及对谱系分化的影响

Early embryonic polarity establishment and implications for lineage differentiation

极性建立是影响早期胚胎发育的关键因素之一。极性建立起始于8细胞胚胎的肌球蛋白磷酸化,磷酸化激活肌动蛋白导致其启动收缩力。随后,肌动蛋白发生重组在每个卵裂球的非接触表面形成富含微绒毛的顶端结构域,并在极性蛋白复合物等的共同作用下形成标志着顶端结构域成熟的肌动球蛋白环。从极性建立的过程可知,顶端结构域的形成受到肌动蛋白相关蛋白以及极性蛋白复合物的影响,并且部分合子基因组激活(zygote genome activation,ZGA)和谱系分化特异性基因也会调控极性建立。在早期胚胎发育过程中,极性建立是第一次细胞谱系分化的基础。它通过影响不对称细胞分裂、谱系分化因子的不对称定位以及Hippo信号通路的活性来调控谱系分离和形态发生。本文对哺乳动物早期胚胎极性建立及对谱系分化影响的相关研究进行了梳理和总结,并讨论了目前已有研究在调控机制和物种方面的不足,以期为阐明早期胚胎极性建立提供线索与系统性视角。

Polarity establishment is one of the key factors affecting early embryonic development.Polarity establishment begins with myosin phosphorylation in the 8-cell embryo,and phosphorylation activates actin leading to its initiation of contractility.Subsequently,actin undergoes reorganization to form an apical domain rich in microvilli on the non-contacting surface of each blastomere,and form the actomyosin ring that marks the maturation of the apical domain in conjunction with polar protein complexes and others.From the process of polarity establishment,it can be seen that the formation of the apical domain is influenced by actin-related proteins and polar protein complexes.Some zygote genome activation(ZGA)and lineage-specific genes also regulate polarity establishment.Polarity establishment underlies the first cell lineage differentiation during early embryonic development.It regulates lineage segregation and morphogenesis by affecting asymmetric cell division,asymmetric localization of lineage differentiation factors,and activity of the Hippo signaling pathway.In this review,we systematically summarize the mechanisms of early embryonic polarity establishment and its impact on lineage differentiation in mammals,and discuss the shortcomings of the currently available studies in terms of regulatory mechanisms and species,thereby providing clues and systematic perspectives for elucidating early embryonic polarity establishment.