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.

项目概要/摘要 基于肌动球蛋白的力产生可将组织塑造成一系列非凡的形状 发展。成功的组织雕刻需要精确调节肌动球蛋白，并且 由此产生的力模式通过组织传递。力传递本身影响收缩 信号传导，导致出现导致组织形状变化的紧急行为。 我们已经证明了动态 RhoA-GTPase 循环在生成肌动球蛋白中的作用 分别是果蝇原肠胚形成和卵子发生过程中的脉冲和波。在每种情况下，我们 鉴定出循环行为所需的 Rho GTP 酶激活蛋白 (RhoGAP)，并且 证明了形态发生中循环的功能重要性。我们的工作已经证明 RhoGTPase 循环在组织内陷和完成细胞质中的要求 从种系支持细胞到卵母细胞的运输。启动这些动态的机制 行为以及它们如何受到组织中力传递的影响仍然未知。 组织中的力传递模式非常复杂且极其动态。我们有 确定了细胞上肌动球蛋白网络在传递力之间的重要性 组织中有数百个细胞，形成机械互连的细胞链。超细胞的 上皮细胞内的肌动球蛋白网可以表现出偏向连接，从而影响组织 机械师。但是，细胞如何确定要链接到哪些邻居尚不清楚，并且理解这一点至关重要 组织形状。此外，响应于消散力的细胞生物学机制 人们对形态发生运动以及它们如何与运动协调知之甚少。 我们将采取多学科和多尺度的方法来了解组织形状 的出现。结合我们可视化和扰乱动态信号通路的能力，我们将 研究细胞“感受到”的力与由此产生的单细胞信号传导模式之间的相互关系 目标是连接分子和组织尺度。我的实验室成员包括生物学家、物理学家、 和工程师。此外，我们在数学方面有优秀的合作者来补充我们的研究 能力。我们准备为我们的理解做出更多的重要贡献 集体细胞行为有助于形态发生。