RhoA- and Cdc42-induced antagonistic forces underlie symmetry breaking and spindle rotation in mouse oocytes

PLoS Biol. 2021 Sep 7;19(9):e3001376. doi: 10.1371/journal.pbio.3001376. eCollection 2021 Sep.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Chromosome Segregation*
  • Female
  • Meiosis*
  • Mice
  • Oocytes / cytology*
  • Spindle Apparatus*
  • cdc42 GTP-Binding Protein
  • rhoA GTP-Binding Protein

Substances

  • Actins
  • cdc42 GTP-Binding Protein
  • rhoA GTP-Binding Protein

Grants and funding

The authors have received funding from the following sources: - Research grant ATIP from the Centre National de la Recherche Scientifique/CNRS (2009; to GH): https://insb.cnrs.fr/fr/atip-avenir - Research grant from the Ligue Contre le Cancer (2015; to GH): https://www.ligue-cancer.net/article/27236_appels-projets-recherche - Academic scholarship from the Society for Reproduction and Fertility (2013; to GH): https://srf-reproduction.org/grants-awards/grants/academic-scholarship-fund/ - PhD scholarship (3 years) from the french Ministry of Research and Higher Education (to BD): https://www.enseignementsup-recherche.gouv.fr/ - PhD scholarship (6 months) from the Fondation pour la Recherche Médicale/FRM (to BD): https://www.frm.org/chercheurs/appel-a-projets-frm The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.