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.

项目总结/文摘