Mechanosensitive mechanisms regulating cellular coordination during tissue morphogenesis and patterning

组织形态发生过程中调节细胞协调的机械敏感性机制 图案化 摘要： 这项研究计划的长期目标是了解和确定机械敏感机制， 在正常组织形态发生和形成模式期间调节细胞与细胞的运动协调。的 特别令人感兴趣的是，机械敏感和拉伸激活蛋白质在转移中发挥的作用， 电流、离子和细胞之间的第二信使，因为这些功能已知对于 在复杂的组织环境中协调细胞通讯。例如，我们的触觉， 血压调节、渗透压调节和平衡均由机械敏感性通道调节 在整个身体。机械敏感性通道的重要性是由许多相关的 机械感觉受损的疾病状态，包括心房颤动，肌肉变性， 心律失常、多囊肾和许多神经系统疾病。尽管如此， 在正常健康的个体细胞水平上， 力以引起细胞信号传导和/或功能的变化。因此，我们的兴趣在于了解 细胞吸收来自机械敏感通道的“数据”，以改变细胞内和细胞间的通讯， 协调组织内的单个细胞运动。为了开展这项工作，我们计划利用我们历史悠久的 斑马鱼发育和组织模式的优势，沿着复杂的三维体外组织 建模分析以了解：1）机械感觉如何影响细胞内信号传导，特别是尽管 转录网络的激活和基因表达的改变，以及2）机械感觉如何影响 细胞间信号传导活动以改变组织的模式。我们将瞄准并利用高度机械敏感的 细胞，如星形胶质细胞，内皮细胞，平滑肌细胞和表皮细胞，为我们的研究， 了解机械感觉在调节基因表达中的普遍作用和细胞类型特异性作用， 细胞运动和细胞间通讯。这些研究将提供基础数据和细胞生物学 为研究机械敏感性通道的社区提供知识。

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.