Mechanisms coordinating cell behaviors within tissues during development

发育过程中协调组织内细胞行为的机制

基本信息

批准号：
10613921
负责人：
Karen Kasza
金额：
$ 38.92万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-04-30
项目状态：
未结题

项目摘要

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.

项目概要/摘要胚胎发育过程中功能组织结构的形成取决于能力细胞协调集体组织水平的运动。我的研究计划的目标是了解细胞如何协同工作共同产生多细胞的形状和结构形态发生过程中的组织。我们目前对形态发生的理解还很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。在此颁奖期间，我们将解决这些挑战并重点关注通过以下方式解决我们理解中的几个关键差距：（1）阐明收缩蛋白和粘附蛋白如何细胞中的机器有助于协调相邻细胞之间的活动，从而产生集体细胞和组织运动，以及（2）剖析机械输入如何与分子输入相结合协调组织内的细胞行为。使用模式生物果蝇，我们采取创新方法在上皮组织的背景下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来控制和量化细胞机器和驱动力这些细胞行为。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机械机制组织。这项工作将为将力学整合到我们对如何理解的理解中提供基础遗传和生化因素控制发育，并可能激发新的控制策略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中自组织的一般原理，提供了对如何不当的见解这些过程的调节会导致人类疾病，并开发新的方法来操纵这些过程具有治疗效果。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Germ fate determinants protect germ precursor cell division by restricting septin and anillin levels at the division plane.

胚芽命运决定因素通过限制分裂平面的隔膜和苯胺水平来保护胚芽前体细胞分裂。

DOI：
发表时间：
2023-11-17
期刊：
影响因子：
0
作者：
Connors, Caroline Q;Mauro, Michael S;Tristian Wiles, J;Countryman, Andrew D;Martin, Sophia L;Lacroix, Benjamin;Shirasu;Dumont, Julien;Kasza, Karen E;Davies, Timothy R;Canman, Julie C
通讯作者：
Canman, Julie C