Mechanoregulation of Cell Functions during Embryogenesis

胚胎发生过程中细胞功能的机械调节

• 批准号: 10638437
• 负责人: SUSAN M PARKHURST
• 金额: $ 19.42万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-20 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10638437
• 关键词: Mechanoregulation; Cell; Functions; during; Embryogenesis

PROJECT SUMMARY Sculpting complex morphological body plans requires the precise orchestration of biophysical and biochemical cues to control the wide range of behaviors demanded of individual cells, as well as groups of cells. Biomechanical forces at the cell level affect the functions of the cell cortex: the plasma membrane and its underlying cortical cytoskeleton. These mechanical cues must be sensed by the cell, then properly acted upon, with the failure to do so leading to abnormal development. Thus, cell mechanoregulation is of fundamental developmental and cell biology interest and significant clinical relevance. The general aim of this proposal is to delineate the contribution of mechanoregulatory signals to cell functions required for normal development, and the consequences of their mis-regulation leading to aberrant cell functions and/or developmental disorders. Drosophila provides an excellent, genetically amenable, model in which to investigate these fundamental processes due to its accessibility to dynamic in vivo imaging and the wealth of state-of-the-art developmental/cell/molecular techniques and reagents available. Our long-term goal is to understand how mechanical cues are sensed, then acted upon, by cells to guide their functions during embryogenesis. To this end, we propose to use the forces generated by cellular wounding as an inducible system in which to study the mechanical properties of the cell cortex, including membrane tension, cortical cytoskeleton dynamics and the integration of these properties. The specific aims of this proposal are: 1) to determine the nature of the scaffold at the embryo cortex involved in tension regulation, and 2) to elucidate the mechanisms regulating actomyosin organization necessary for generating contractile forces within cells. The information gathered in these studies will provide new insight into the mechanical characteristics of the cell, as well as provide a better understanding of how the cell interprets the intrinsic and extrinsic forces acting upon it to orchestrate complex functions and interactions.

项目摘要 塑造复杂的形态身体计划需要生物物理和 控制个体细胞和群体所需的广泛行为的生化线索 信元细胞水平的生物力学力影响细胞皮层的功能： 膜及其下面的皮质细胞骨架。这些机械信号必须被细胞感知， 然后采取适当的行动，不这样做会导致不正常的发展。因此，Cell 机械调节具有基本的发育和细胞生物学意义， 本案无关这项建议的总体目标是阐明机械调节的贡献， 正常发育所需的细胞功能的信号，以及它们的错误调节的后果 导致异常的细胞功能和/或发育障碍。果蝇提供了一个极好的， 遗传上可行的，模型，其中调查这些基本过程，由于其 可获得动态体内成像和丰富的最先进的发育/细胞/分子 技术和试剂。我们的长期目标是了解机械提示是如何 在胚胎发生过程中，细胞感知并采取行动来指导它们的功能。为此我们 我建议使用细胞创伤产生的力量作为一个诱导系统，在其中研究 细胞皮层的力学性质，包括膜张力、皮层细胞骨架动力学 以及这些属性的整合。该提案的具体目标是：1）确定 胚胎皮层中涉及张力调节的支架的性质，以及2）为了阐明 调节肌动球蛋白组织产生收缩力所必需的机制 细胞在这些研究中收集的信息将提供新的见解， 细胞的特性，以及提供更好地了解细胞如何解释细胞的功能。 内在和外在的力量作用于它，以协调复杂的功能和相互作用。