Abstract

Cytokinesis occurs at the end of mitosis to divide the cell into two daughter cells. An actomyosin contractile ring forms at the equatorial cortex and ingresses to pinch in the cytosol and membrane. Anillin is a highly conserved protein that binds to components of the ring, mitotic spindle and membrane, and is a key regulator of cytokinesis. The division plane occurs perpendicular to the axis of asymmetry in epithelial cells to ensure that each daughter cell inherits apicobasal polarity. However, these cells undergo dramatic shape changes that involve reorganization of the cytoskeleton during mitosis, and it is not clear how the daughter cells re-establish polarity. Interestingly, contractile ring ingression occurs asymmetricaly in epithelial cells, where one part of the ring appears to move faster and closes near the apical surface. Recent studies using Drosophila epithelial tissue showed that asymmetric ingression occurs due to forces generated near the apical surface of dividing cells, through adhesion with neighbouring cells. We studied cytokinesis in mammalian epithelial cells using Madin Darby Canine Kidney (MDCK) epithelial cells as a model system. Interestingly, we observed that MDCK cells with none or fewer than four neighbours displayed asymmetric ingression, while cells with four or more neighbours were more likely to ingress symmetrically, suggesting that both intrinsic and extrinsic mechanisms influence contractile ring ingression. When induced to form cysts, ingression varied depending on the location of cells within the cyst. The localization of myosin and anillin were uncoupled in asymmetrically dividing MDCK cells, with anillin being more enriched on the ingressing cortex. Anillin may have an important role in asymmetric ingression, since its asymmetric distribution correlated with asymmetric ingression, and its depletion caused cells to ingress more randomly. These results suggest that mammalian epithelial cells possess intrinsic mechanisms for asymmetric ingression, and extrinsic forces applied by neighbouring cells influence their ingression.