Tissue morphogenesis: From signals to forces

组织形态发生：从信号到力量

• 批准号: 10330672
• 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/10330672
• 关键词: Actomyosin; Affect; Behavior; Biological; Cells; Complex; Congenital Abnormality; Cytoskeleton; Development; Drosophila genus; Engineering; Epithelial; 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; Work; base; behavior influence; cell behavior; gastrulation; insight; member; multidisciplinary; response; 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.

项目总结/摘要 肌动球蛋白为基础的力量产生雕塑组织成一个显着的阵列的形状， 发展成功的组织塑形需要肌动球蛋白被精确调节， 所产生的力模式被传递通过组织。力传递本身影响收缩性 信号传导，导致导致组织形状改变的紧急行为。 我们已经证明了动态RhoA-GT循环在产生肌动球蛋白中的作用， 脉冲和波在果蝇原肠胚和卵子发生。在每一种情况下，我们 鉴定了Rho GT3激活蛋白（RhoGAP），其是循环行为所需的， 证明了形态发生中循环的功能重要性。我们的工作证明了 RhoGT 3循环在组织内陷中的需要和细胞质内 从生殖支持细胞到卵母细胞的转运。启动这些动态的机制 行为以及它们如何受到组织中的力传递的影响仍然是未知的。 组织中的力传递模式是复杂的且极其动态的。我们有 确定了超细胞肌动球蛋白网在传递力之间的重要性， 一个组织中有数百个细胞，它们形成了机械连接的细胞链。超细胞 上皮内的肌动球蛋白网可以表现出偏向性连接，这影响了组织 力学但是，细胞如何决定与哪些邻居链接是未知的，这对理解至关重要 组织形状此外，细胞生物学机制，消散力，以响应 对形态发生运动以及它们如何与运动协调还知之甚少。 我们将采取多学科和多尺度的方法来了解组织形状 出现。结合我们可视化和干扰动态信号通路的能力，我们将 研究细胞“感受”到的力与产生的单细胞信号模式之间的相互联系 其目标是在分子和组织尺度之间架起桥梁。我实验室的成员包括生物学家，物理学家， 和工程师。此外，我们在数学方面有优秀的合作者，以补充我们的研究 能力的我们准备作出更多的重要贡献，以了解如何 集体细胞行为有助于形态发生。