Tissue morphogenesis: From signals to forces

组织形态发生：从信号到力量

• 批准号: 10543998
• 负责人: Adam Christopher Martin
• 金额: $ 54.35万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10543998
• 关键词: Actomyosin; Affect; Behavior; Biological; Cells; Complex; Congenital Abnormality; Cytoplasm; Cytoskeleton; Development; Drosophila genus; Engineering; Epithelium; Exhibits; Generations; Goals; Guanosine Triphosphate Phosphohydrolases; Incidence; Link; Mathematics; Mechanics; Molecular; Morphogenesis; Movement; Oocytes; Oogenesis; Pattern; Physiologic pulse; Regulation; Research; Role; Shapes; Signal Pathway; Signal Transduction; Supporting Cell; Tissues; Visualization; Work; cell behavior; gastrulation; insight; member; multidisciplinary; response; rho GTP-Binding Proteins; rho GTPase-activating protein; transmission process

Project Summary/Abstract Actomyosin-based force generation sculpts tissues into a remarkable array of shapes during development. Successful tissue sculpting requires that actomyosin is precisely regulated and that the resulting force patterns are transmitted across the tissue. Force transmission itself affects contractile signaling, resulting in emergent behaviors that result in tissue shape change. We have demonstrated the role of dynamic RhoA-GTPase cycling in generating actomyosin pulses and waves in Drosophila gastrulation and oogenesis, respectively. In each of these cases, we identified a Rho GTPase activating protein (RhoGAP) that is required for cycling behavior and demonstrates the functional importance for the cycling in morphogenesis. Our work has demonstrated the requirement of RhoGTPase cycling in tissue invagination and the completion of cytoplasmic transport from germline support cells to the oocyte. The mechanisms that initiate these dynamic behaviors and how they are influenced by force transmission in a tissue are still unknown. Patterns of force transmission in a tissue are complex and extremely dynamic. We have identified the importance of supracellular actomyosin meshworks in transmitting forces between hundreds of cells in a tissue, which forms chains of mechanically interconnected cells. Supracellular actomyosin meshworks within epithelia can exhibit biased connections, which influence tissue mechanics. But, how a cell determines which neighbors to link to is unknown and critical to understand tissue shape. Furthermore, the cell biological mechanisms that dissipate forces in response to morphogenetic movements and how they are coordinated with movement are poorly understood. We will undertake a multidisciplinary and multiscale approach to understand tissue shape emergence. Combining our ability to visualize and perturb dynamic signaling pathways we will investigate the interconnection between forces `felt' by cells and resulting single cell signaling patterns with the goal of bridging molecular and tissue scales. Members of my lab include biologists, physicists, and engineers. In addition, we have excellent collaborators in Mathematics to supplement our research capabilities. We are poised to make additional important contributions to our understanding of how collective cell behaviors contribute to morphogenesis.

项目摘要/摘要 基于肌动球蛋白的力产生将组织雕刻成一系列显着的形状 发展。成功的组织雕刻要求肌动蛋白受到精确调节，并且 产生的力模式在整个组织中传播。力传递本身会影响收缩 信号传导，导致紧急行为导致组织形状变化。 我们已经证明了动态RhoA-GTPase循环在产生肌动球蛋白中的作用 果蝇胃和卵子发生的脉冲和波。在每种情况下，我们 确定了循环行为和 证明了对形态发生中循环的功能重要性。我们的工作已经证明了 Rhogtpase循环在组织内幕和胞质的完成中的要求 从种系支撑细胞到卵母细胞的运输。启动这些动态的机制 行为及其如何受组织在组织中的影响仍然未知。 组织中力传播的模式是复杂的，并且极具动态性。我们有 确定了细胞上肌球蛋白网格工程在传输力之间的重要性 组织中的数百个细胞形成机械互连细胞的链。细胞上 上皮中的肌动球蛋白网格工程可以表现出偏见的连接，从而影响组织 力学。但是，单元格如何确定要链接到哪个邻居是未知和重要的 组织形状。此外，响应响应力的细胞生物学机制 形态发生运动及其与运动如何协调的方式知之甚少。 我们将采用多学科和多尺度的方法来理解组织形状 出现。结合我们可视化和扰动动态信号通路的能力，我们将 研究通过细胞“感觉”力与产生的单细胞信号模式之间的互连 以弥合分子和组织尺度的目的。我的实验室成员包括生物学家，物理学家， 和工程师。此外，我们还有数学上的出色合作者来补充我们的研究 功能。我们准备为我们对如何理解做出其他重要贡献 集体细胞行为有助于形态发生。