Cytokinesis-dependent twisting of HMR-1/Cadherin regulates the first left-right symmetry-breaking event in Caenorhabditis elegans

Diverse mechanisms for establishing cellular- and organismal-level left-right (L-R) asymmetry emerged during the evolution of bilateral animals, including cilia-based and actomyosin-dependent mechanisms. In pond snails and Caenorhabditis elegans , cell division plays a critical role in regulating both levels of L-R asymmetries. However, the precise mechanism by which cell division breaks cellular-level L-R symmetry remains elusive. Here, we show that cytokinesis-induced cortical flow twists the cell-cell adhesion pattern, which in turn controls the L-R asymmetrical constriction of the contractile ring, thereby breaking the first L-R body symmetry in C. elegans . During the second mitosis of C. elegans embryos, we discovered the twisting of the HMR-1/cadherin patch at the cell-cell contact site. The HMR-1 patch twisting occurs within a few minutes upon cytokinesis onset, with individual cadherin foci within the patch exhibits directional flow and coalescence. This cell type exhibits chiral cortical flow, characterized by counter-rotational surface flows in the two halves of the dividing cell. We found that this chiral cortical flow plays a critical role in regulating HMR-1 patch twisting by inducing cadherin flow. As the HMR-1 patch twists, the contractile ring preferentially associates with HMR-1 on the right side of the embryo. We demonstrate that HMR-1 patch twisting regulates the L-R asymmetric ring closure. This study uncovers an interplay between three fundamental cellular processes—cell-cell adhesion, cytokinesis, and cell polarity— mediated by cadherin flow, shedding light on cadherin flow’s role in cellular patterning during development.