RT Journal Article SR Electronic T1 RhoA- and Ran-induced antagonistic forces underlie symmetry breaking and spindle rotation in mouse oocytes JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.10.20.348045 DO 10.1101/2020.10.20.348045 A1 Benoit Dehapiot A1 Raphaël Clément A1 Anne Bourdais A1 Sébastien Huet A1 Guillaume Halet YR 2020 UL http://biorxiv.org/content/early/2020/10/21/2020.10.20.348045.abstract AB Mammalian oocyte meiotic divisions are highly asymmetric and produce a large haploid gamete and two small polar bodies. This relies on the ability of the cell to break symmetry and position its spindle close to the cortex before the anaphase occurs. In metaphase II arrested mouse oocytes, the spindle is actively maintained close and parallel to the cortex, until the fertilization triggers the sister chromatids segregation and the rotation of the spindle. The latter must indeed reorient perpendicular to the cortex to enable the 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 the spindle rotation results from two antagonistic forces. First, an inward contraction of the cytokinesis furrow dependent on RhoA signaling and second, an outward attraction exerted on both lots of chromatids by a RanGTP dependent polarization of the actomyosin cortex. By combining live segmentation and tracking with numerical modelling, 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 lot of chromatids that eventually gets discarded are biologically predetermined.Competing Interest StatementThe authors have declared no competing interest.