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Unravelling the cytokinesis-dependent mechanism underlying the first left-right symmetry breaking event in Caenorhabditis elegans Khor, Mi Jing

Abstract

During evolution, bilateral animals developed multiple mechanisms to break left-right (L-R) body symmetry, including cilia-based and actomyosin-dependent mechanisms. Cell division plays a key role in breaking L-R symmetry in pond snails and Caenorhabditis elegans. However, the precise mechanism by which cell division establishes L-R asymmetry remains elusive. In this thesis, I reveal that cytokinesis-induced cortical flow regulates the cell-cell adhesion pattern, which subsequently influences the asymmetric constriction of the contractile ring, thereby initiating the first L-R body symmetry in C. elegans. During the second mitosis of C. elegans embryos, I found that the HMR-1/cadherin patch undergoes a twisting motion at the cell-cell contact site within a few minutes upon anaphase onset. The rapid increase of signal intensity in the direction of the twist suggests lateral movement of HMR-1 on the cell-cell contact membrane. I discovered that cortical flow—a concerted movement of the cell cortex—plays a key role in the twisting of the HMR-1 patch. During the second mitosis, the two halves of the dividing cell exhibit counter rotating cortical flows termed chiral cortical flow. I found that this chiral cortical flow is essential for the HMR-1 patch twisting. As the HMR-1 patch twists, the contractile ring preferentially associates with cadherin on the right side of the embryo, indicating its involvement in L-R asymmetric contractile ring closure. Furthermore, the loss and reversal of HMR-1 patch twisting consistently correlate with changes in contractile ring closure asymmetry. This thesis unveils a novel interaction between cell-cell adhesion and cytokinesis, highlighting their role in breaking L-R symmetry during development.

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Attribution-NonCommercial-NoDerivatives 4.0 International