Mechanosensitive mechanisms regulating cellular coordination during tissue morphogenesis and patterning Abstract: The long-term goal of this research program is to understand and identify mechanosensitive mechanisms that regulate cell-to-cell coordination of movements during normal tissue morphogenesis and patterning. Of particular interest, is the role that mechanosensitive and stretch activated proteins play in the transfer of electrical currents, ions, and second messengers between cells, as these functions are known to be critical for coordination of cellular communication within a complex tissue environment. For instance, our sense of touch, regulation of blood pressure, osmotic regulation, and balance are all regulated by mechanosensitive channels throughout the body. The importance of mechanosensitive channels is underscored by the association of many disease states with compromised mechanosensation, including atrial fibrillation, muscular degeneration, arrhythmias, polycystic kidney disease, and numerous neural diseases. Despite this, a relatively small amount is known at the level of normal, healthy individual cells about how mechanosensitive channels go from sensing force to eliciting changes in cellular signaling and/or function. Our interest therefore lies in understanding how cells assimilate ?data? from mechanosensitive channels to alter intra- and inter- cellular communication and coordinate individual cellular movements within tissues. To carry out this work, we plan to utilize our historic strengths in zebrafish development and tissue patterning along with sophisticated 3-dimensional in vitro tissue modeling assays to understand: 1) how mechanosensation affects intracellular signaling, particularly though the activation of transcriptional networks and altered gene expression, and 2) how mechanosensation affects intercellular signaling activities to alter patterning of tissues. We will target and utilize highly mechanosensitive cells, such as astrocytes, endothelial cells, smooth muscle cells, and epidermal cells, for our studies to understand both generalizable and cell type specific roles of mechanosensation in regulating gene expression, cellular motility, and cell-to-cell communication. These studies will provide fundamental data and cell biological knowledge to the community studying mechanosensitive channels.
The importance of mechanosensitive channels to human health is underscored by the association of many disease states with compromised mechanosensation, including atrial fibrillation, muscular degeneration, arrhythmias, polycystic kidney disease, and numerous neural diseases. Therefore, it is the goal of this work is to understand both generalizable and cell type specific roles of mechanosensation in regulating gene expression, cellular motility, and cell-to-cell communication.
