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.
