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

Benoit Dehapiot (1, 2) , Raphael Clement (2) , Anne Bourdais (1) , Virginie Carrière (1) , Sébastien Huet (1) , Guillaume Halet (1)

1 IGDR - Institut de Génétique et Développement de Rennes
2 IBDM - Institut de Biologie du Développement de Marseille

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.

Domaines: Sciences du Vivant [q-bio]

Benoit Dehapiot, Raphael Clement, Anne Bourdais, Virginie Carrière, Sébastien Huet, et al.. RhoA- and Cdc42-induced antagonistic forces underlie symmetry breaking and spindle rotation in mouse oocytes. PLoS Biology, 2021, 19 (9), pp.e3001376. ⟨10.1371/journal.pbio.3001376⟩. ⟨hal-03368104⟩