Wnt regulates myosin flow to promote cytokinesis

Context Cytokinesis, the division of one cell into two, is crucial for an animal’s development and healthy life. Errors in this process can lead to cell death or mutations. Research on cytokinesis has largely focused on simple, single cell models systems, and has led to the identification of key proteins and processes. However, emerging evidence suggests that some cell types show variations from these models and clinical studies have further demonstrated this variability, and the limitations of our current models. Challenge In this wider context of reassessing our understanding of cytokinesis, we must now use biological model systems that allow us to demonstrate how cytokinesis may vary between different types of cells, and where the effects of cell environments can also be recognised and measured. To address this challenge, we have established embryos from the round worm, Caenorhabditis elegans, as an ideal tool to study cytokinesis in a complex environment. We have previously shown that specific cells in the embryo can divide successfully despite depletion of what were previously thought to be essential proteins (f-actin polymerase and f-actin). This successful division requires signalling from an adjacent cell and our preliminary data indicate the involvement of the ‘Wnt pathway’ a cell signalling pathway important for cell fate determination during development and frequently goes wrong in tumours. In this project, we seek to understand Wnt’s ability to promote successful cytokinesis in neighbouring cells. Aims and Objectives We aim to understand the molecular requirements for cytokinesis using the C. elegans model system, by manipulation of signalling pathways and tracking of cellular components in real-time during division. Our preliminary data indicate that Wnt signalling controls the position of the ‘mitotic spindle,’ a key cellular structure that signals where the cell will divide, and that this impacts other cytokinesis components. We will investigate the role of Wnt signalling in promoting cytokinesis with three specific objectives: To dissect the ability of Wnt signalling to enable successful EMS cytokinesis. To determine how Wnt signalling regulates spindle position during cell division. To identify how Wnt regulation of spindle position enables cytokinesis. Potential Applications and Benefits Cytokinesis is a central biological process, and its regulation by contextual factors such as cellular signalling is crucial to understanding the complexity of cell division in multicellular organisms. By elucidating how Wnt signalling promotes successful cytokinesis, this project will advance the paradigm of context-specific cell biology, showing that even fundamental processes like cytokinesis can vary depending on the cellular environment. These insights have significant implications for understanding diseases, such as cancer, where both cytokinesis and signalling pathways are often dysregulated. Relevance to BBSRC’s Long-Term Research and Innovation Priorities This project aligns with the BBSRC’s objective of advancing the frontiers of bioscience discovery by expanding our understanding of the rules of life. By integrating knowledge of cell signalling with the mechanics of cell division, it will deliver an integrated understanding of health. Insights gained from this work may also inform therapeutic strategies for diseases characterized by dysregulation of essential biological processes.