Two RhoGEF isoforms with distinct localisation act in concert to control asymmetric cell division

Abstract

Cytokinesis is essential for the partitioning of cellular contents into daughter cells. It relies on the formation of an acto-myosin contractile ring, whose constriction induces the ingression of the cleavage furrow between the segregated chromatids. Rho1 GTPase and its RhoGEF (Pbl) are essential for this process as they drive the assembly and constriction of the contractile ring. However, how Rho1 is regulated to sustain efficient furrow ingression while maintaining correct furrow position remains poorly defined. Here, we show that during asymmetric division of Drosophila neuroblasts, Rho1 is controlled by two Pbl isoforms with distinct localisation. Spindle midzone- and furrow-enriched Pbl-A focuses Rho1 at the furrow to sustain efficient ingression, while Pbl-B pan-plasma membrane localization promotes the broadening of Rho1 activity and the subsequent enrichment of cortical myosin. This enlarged zone of Rho1 activity becomes essential to adjust furrow position during ingression, thereby preserving correct daughter cell size asymmetry. Our work highlights how the use of isoforms with distinct localisation patterns provides robustness to an essential process.