Tissue morphogenesis: From signals to forces

项目摘要/摘要 基于肌动球蛋白的力生成在过程中将组织雕刻成一系列引人注目的形状 发展。成功的组织塑造需要肌动球蛋白受到精确的调控，而且 由此产生的力模式在整个组织中传递。力传递本身会影响收缩 信号，导致导致组织形状变化的紧急行为。 我们已经证明了动态RhoA-GTP酶循环在肌动球蛋白生成中的作用 果蝇原肠发育和卵子发生中的脉冲和波。在每一种情况下，我们 发现了一种Rho GTP酶激活蛋白(RhoGAP)，它是循环行为所必需的，并且 证明了循环在形态发生中的功能重要性。我们的工作证明了 RhoGTPase循环在组织内陷和细胞质完成中的要求 从生殖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力在组织中传递的影响仍是未知的。 力在组织中的传递模式是复杂和极其动态的。我们有 确认了超细胞肌球蛋白网络在相互间传力中的重要性 组织中的数百个细胞，形成机械连接的细胞链。超细胞 上皮细胞内的肌动球蛋白网络可以表现出偏向连接，从而影响组织。 机械师。但是，像元如何确定要链接到哪些邻域是未知的，也是理解这一点的关键 组织形状。此外，细胞生物学机制驱散力量，以响应 形态发生运动以及它们是如何与运动相协调的，人们知之甚少。 我们将采取多学科和多尺度的方法来了解组织形状 浮现。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和由此产生的单细胞信号模式之间的相互联系 目标是在分子和组织规模之间架起桥梁。我的实验室成员包括生物学家、物理学家、 和工程师。此外，我们有优秀的数学合作者来补充我们的研究 能力。我们准备作出更多重要贡献，帮助我们理解 集体细胞行为有助于形态发生。

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.