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机制 图案化 摘要： 这项研究计划的长期目标是了解和识别机械敏感机制 在正常的组织形态形成和构图过程中调节细胞间的运动协调。的 特别令人感兴趣的是机械敏感蛋白和拉伸激活蛋白在运输过程中所起的作用 电流、离子和细胞之间的第二信使，因为这些功能对 在复杂的组织环境中协调细胞通讯。例如，我们的触觉， 血压的调节、渗透调节和平衡都是由机械敏感通道调节的。 遍及全身。机械敏感通道的重要性被许多 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、多囊肾病和许多神经疾病。尽管如此，相对较少的 在正常、健康的个体细胞水平上已知机械敏感通道是如何从感知 强迫引起细胞信号和/或功能的改变。因此，我们的兴趣在于了解如何 细胞同化来自机械敏感通道的数据，以改变细胞内和细胞间的通信和 协调个体细胞在组织内的运动。为了开展这项工作，我们计划利用我们的历史经验 斑马鱼发育和组织构图的优势以及复杂的三维体外组织 建模分析旨在了解：1)机械感觉如何影响细胞内信号传递，尤其是 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 改变组织图案的细胞间信号活动。我们将瞄准并利用高度机械敏感性 细胞，如星形胶质细胞、内皮细胞、平滑肌细胞和表皮细胞，用于我们的研究 理解机械感觉在调节基因表达中的普遍作用和细胞类型特有的作用， 细胞的运动和细胞间的通讯。这些研究将提供基础数据和细胞生物学 知识向社会学习机械敏感通道。

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.