Pomp Oz, Lim Hui Yi Grace, Skory Robin M, Moverley Adam A, Tetlak Piotr, Bissiere Stephanie, Plachta Nicolas
Department of Cell and Developmental Biology, Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Institute of Molecular and Cell Biology, ASTAR, Singapore, Singapore.
Nat Cell Biol. 2022 Feb;24(2):155-167. doi: 10.1038/s41556-021-00826-3. Epub 2022 Jan 31.
During mammalian development, the first asymmetric cell divisions segregate cells into inner and outer positions of the embryo to establish the pluripotent and trophectoderm lineages. Typically, polarity components differentially regulate the mitotic spindle via astral microtubule arrays to trigger asymmetric division patterns. However, early mouse embryos lack centrosomes, the microtubule-organizing centres (MTOCs) that usually generate microtubule asters. Thus, it remains unknown whether spindle organization regulates lineage segregation. Here we find that heterogeneities in cell polarity in the early 8-cell-stage mouse embryo trigger the assembly of a highly asymmetric spindle organization. This spindle arises in an unusual modular manner, forming a single microtubule aster from an apically localized, non-centrosomal MTOC, before joining it to the rest of the spindle apparatus. When fully assembled, this 'monoastral' spindle triggers spatially asymmetric division patterns to segregate cells into inner and outer positions. Moreover, the asymmetric inheritance of spindle components causes differential cell polarization to determine pluripotent versus trophectoderm lineage fate.
在哺乳动物发育过程中，最初的不对称细胞分裂将细胞分隔到胚胎的内部和外部位置，以建立多能性和滋养外胚层谱系。通常情况下，极性成分通过星状微管阵列差异调节有丝分裂纺锤体，从而触发不对称分裂模式。然而，早期小鼠胚胎缺乏中心体，即通常产生微管星状体的微管组织中心（MTOC）。因此，纺锤体组织是否调节谱系分离仍不清楚。在这里，我们发现8细胞期早期小鼠胚胎中的细胞极性异质性触发了高度不对称纺锤体组织的组装。这种纺锤体以一种不寻常的模块化方式出现，从顶端定位的、非中心体的MTOC形成单个微管星状体，然后将其与纺锤体装置的其余部分连接起来。当完全组装好时，这种“单星体”纺锤体触发空间不对称分裂模式，将细胞分隔到内部和外部位置。此外，纺锤体成分的不对称遗传导致细胞极化差异，从而决定多能性与滋养外胚层谱系命运。
