Mechanoregulation of Cell Functions during Embryogenesis

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PROJECT SUMMARY Sculpting complex morphological body plans requires the precise orchestration of biophysical and biochemical cues to control the wide range of behaviors demanded of individual cells, as well as groups of cells. Biomechanical forces at the cell level affect the functions of the cell cortex: the plasma membrane and its underlying cortical cytoskeleton. These mechanical cues must be sensed by the cell, then properly acted upon, with the failure to do so leading to abnormal development. Thus, cell mechanoregulation is of fundamental developmental and cell biology interest and significant clinical relevance. The general aim of this proposal is to delineate the contribution of mechanoregulatory signals to cell functions required for normal development, and the consequences of their mis-regulation leading to aberrant cell functions and/or developmental disorders. Drosophila provides an excellent, genetically amenable, model in which to investigate these fundamental processes due to its accessibility to dynamic in vivo imaging and the wealth of state-of-the-art developmental/cell/molecular techniques and reagents available. Our long-term goal is to understand how mechanical cues are sensed, then acted upon, by cells to guide their functions during embryogenesis. To this end, we propose to use the forces generated by cellular wounding as an inducible system in which to study the mechanical properties of the cell cortex, including membrane tension, cortical cytoskeleton dynamics and the integration of these properties. The specific aims of this proposal are: 1) to determine the nature of the scaffold at the embryo cortex involved in tension regulation, and 2) to elucidate the mechanisms regulating actomyosin organization necessary for generating contractile forces within cells. The information gathered in these studies will provide new insight into the mechanical characteristics of the cell, as well as provide a better understanding of how the cell interprets the intrinsic and extrinsic forces acting upon it to orchestrate complex functions and interactions.