Mechanisms coordinating cell behaviors within tissues during development

项目总结/摘要 胚胎发育过程中功能性组织结构的形成取决于 来协调集体组织水平的运动。我的研究项目的目标是 了解细胞如何共同工作，共同产生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有限 通过概念和技术障碍来剖析机械和分子输入， 共同协调细胞行为。在此次颁奖期间，我们将应对这些挑战，并专注于 解决我们理解中的几个关键差距：（1）阐明收缩和粘附蛋白如何 细胞中的机制帮助协调相邻细胞之间的活动，产生集体细胞 和组织运动，以及（2）解剖机械输入如何与分子输入整合， 协调组织内的细胞行为。利用模式生物果蝇，我们 采取创新的方法来解决上皮组织中的这些问题， 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 并使用新技术来控制和量化细胞机制和驱动细胞的力量， 这些细胞行为。这些技术与定量建模相结合，将使我们能够 剖析在多细胞内协调细胞行为的分子和机械机制 组织中这项工作将提供一个基础，将力学融入我们的理解， 遗传和生化因素控制发展，并可能激发新的战略， 在体内和体外的组织形状和结构。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背后的机制可以阐明 生物系统自组织的一般原理，提供了对如何不适当的洞察力， 这些过程的调节导致人类疾病，并开发新的方法来操纵 这些过程的治疗效益。

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.