Aix Marseille Université, CNRS, IBDM-UMR7288, Turing Center for Living Systems, Marseille, France.
Univ Rennes, CNRS, IGDR-UMR 6290, Rennes, France.
PLoS Biol. 2021 Sep 7;19(9):e3001376. doi: 10.1371/journal.pbio.3001376. eCollection 2021 Sep.
Mammalian oocyte meiotic divisions are highly asymmetric and produce a large haploid gamete and 2 small polar bodies. This relies on the ability of the cell to break symmetry and position its spindle close to the cortex before anaphase occurs. In metaphase II-arrested mouse oocytes, the spindle is actively maintained close and parallel to the cortex, until fertilization triggers sister chromatid segregation and the rotation of the spindle. The latter must indeed reorient perpendicular to the cortex to enable cytokinesis ring closure at the base of the polar body. However, the mechanisms underlying symmetry breaking and spindle rotation have remained elusive. In this study, we show that spindle rotation results from 2 antagonistic forces. First, an inward contraction of the cytokinesis furrow dependent on RhoA signaling, and second, an outward attraction exerted on both sets of chromatids by a Ran/Cdc42-dependent polarization of the actomyosin cortex. By combining live segmentation and tracking with numerical modeling, we demonstrate that this configuration becomes unstable as the ingression progresses. This leads to spontaneous symmetry breaking, which implies that neither the rotation direction nor the set of chromatids that eventually gets discarded are biologically predetermined.
哺乳动物卵母细胞减数分裂高度不对称，产生一个大的单倍体配子和 2 个小的极体。这依赖于细胞打破对称性的能力，并在后期发生之前将其纺锤体定位到靠近皮层。在中期 II 期阻滞的小鼠卵母细胞中，纺锤体被积极地维持靠近并平行于皮层，直到受精触发姐妹染色单体分离和纺锤体的旋转。后者确实必须重新定向垂直于皮层，以在极体底部完成胞质分裂环闭合。然而，对称性破坏和纺锤体旋转的机制仍然难以捉摸。在这项研究中，我们表明纺锤体旋转是由 2 种拮抗力引起的。首先，依赖于 RhoA 信号的胞质分裂沟的向内收缩，其次，由肌动球蛋白皮层的 Ran/Cdc42 依赖性极化对两组染色单体施加的向外吸引力。通过将实时分割和跟踪与数值建模相结合，我们证明随着入侵的进行，这种构型变得不稳定。这导致自发的对称性破坏，这意味着旋转方向和最终被丢弃的染色单体都不是生物预先确定的。
