Mechanosensitive mechanisms regulating cellular coordination during tissue morphogenesis and patterning

组织形态发生和模式形成过程中调节细胞协调的机械敏感机制

• 批准号: 10620282
• 负责人: Amber Nicole Stratman
• 金额: $ 42.63万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10620282
• 关键词: 3-Dimensional; Affect; Arrhythmia; Astrocytes; Atrial Fibrillation; Biological; Biological Assay; Cell Communication; Cells; Communication; Communities; Complex; Data; Disease; Endothelial Cells; Environment; Equilibrium; Gene Expression; Goals; Health; Human; In Vitro; Individual; Ions; Knowledge; Morphogenesis; Movement; Muscle; Normal tissue morphology; Osmosis; Pattern; Play; Polycystic Kidney Diseases; Proteins; Regulation; Research; Role; Second Messenger Systems; Signal Transduction; Smooth Muscle Myocytes; Stretching; Tissue Model; Tissues; Touch sensation; Transcriptional Activation; Work; blood pressure regulation; cell motility; cell type; intercellular communication; interest; neural; programs; zebrafish development

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.

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 抽象的： 该研究计划的长期目标是了解和识别机械敏感机制 在正常组织形态发生和模式形成过程中调节细胞间的运动协调。 特别感兴趣的是机械敏感蛋白和拉伸蛋白激活在转移中发挥的作用 细胞之间的电流、离子和第二信使，因为这些功能已知对细胞至关重要 复杂组织环境中细胞通讯的协调，例如我们的触觉， 血压调节、渗透调节和平衡均由机械敏感通道调节 许多组织的关联强调了机械敏感通道的重要性。 机械感觉受损的疾病状态，包括心房颤动、肌肉变性、 尽管如此，心律失常、多囊肾病和许多神经系统疾病的数量相对较少。 在正常、健康的个体细胞水平上已知机械敏感通道如何从传感 因此，我们的兴趣在于了解如何引起细胞信号和/或功能的变化。 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， 为了开展这项工作，我们计划利用我们的历史知识。 斑马鱼发育和组织模式以及复杂的 3 维体外组织的优势 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 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 我们将瞄准并利用高度机械敏感性的细胞间信号活动来改变组织的模式。 细胞，如星形胶质细胞、内皮细胞、平滑肌细胞和表皮细胞，供我们研究 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， 这些研究将提供基础数据和细胞生物学。 向社区研究机械敏感通道的知识。