Mechanisms coordinating cell behaviors within tissues during development

项目摘要/摘要 胚胎发育过程中功能性组织结构的形成依赖于 以协调组织水平的集体运动。我的研究计划的目标是 了解细胞如何共同工作以共同生成多细胞的形状和结构 在形态发生过程中的组织。我们目前对形态发生的理解是有限的 通过剖析机械和分子输入的概念和技术障碍， 共同协调细胞的行为。在这个奖项中，我们将应对这些挑战，并将重点放在 通过以下方式解决我们理解中的几个关键差距：(1)阐明收缩和黏附蛋白如何 细胞中的机制有助于协调相邻细胞之间的活动，以产生集体细胞 和组织运动，以及(2)剖析机械输入和分子输入如何结合在一起 协调组织内的细胞行为。利用模式生物黑腹果蝇，我们正在 在上皮组织的背景下采取创新的方法来解决这些问题 形态发生。为了使我们能够剖析协调细胞行为的机制，我们正在开发 并使用新技术控制和量化驱动细胞的机械和力 这些细胞行为。这些技术与定量建模相结合，将使我们能够 剖析协调多细胞内细胞行为的分子和力学机制 纸巾。这项工作将为将力学集成到我们对如何 遗传和生化因素控制着发育，并可能激发新的控制策略 体内和体外的组织形态和结构。更广泛地说，我们开发的工具和框架将 使我们能够研究在广泛的多细胞环境中协调细胞行为的机制 流程。更好地理解集体细胞行为的潜在机制可以阐明 生物系统中自组织的一般原理，提供了对如何不适当的洞察 对这些过程的调控会导致人类疾病，并开发新的方法来操纵 这些过程对治疗有好处。

PROJECT SUMMARY/ABSTRACT The formation of functional tissue architectures during embryonic development depends on the ability of cells to orchestrate collective tissue-level movements. The goal of my research program is to understand how cells work together to collectively generate the shape and structure of multicellular tissues in the process of morphogenesis. Our current understanding of morphogenesis has been limited by conceptual and technological barriers to dissecting the mechanical and molecular inputs that together coordinate cell behaviors. During this award, we will address these challenges and focus on resolving several key gaps in our understanding by: (1) elucidating how contractile and adhesive protein machineries in cells help coordinate activities between neighboring cells to give rise to collective cell and tissue movements and (2) dissecting how mechanical inputs integrate with molecular inputs to coordinate cell behaviors within tissues. Using the model organism Drosophila melanogaster, we are taking innovative approaches to address these questions in the context of epithelial tissue morphogenesis. To enable us to dissect mechanisms that coordinate cell behaviors, we are developing and using new technologies for controlling and quantifying the cell machineries and forces that drive these cell behaviors. These techniques, in combination with quantitative modeling, will allow us to dissect the molecular and mechanical mechanisms that coordinate cell behaviors within multicellular tissues. This work will provide a foundation for integrating mechanics into our understanding of how genetic and biochemical factors control development and may motivate new strategies for controlling tissue shape and structure in vivo and in vitro. More broadly, the tools and framework we develop will enable us to investigate the mechanisms that coordinate cell behaviors in a broad range of multicellular processes. A better understanding of the mechanisms underlying collective cell behaviors can elucidate general principles of self-organization in biological systems, provide insight into how improper regulation of these processes leads to human disease, and develop new approaches to manipulate these processes for therapeutic benefit.