Sliding vertex behaviors during epithelial morphogenesis and tissue elongation

上皮形态发生和组织伸长期间的滑动顶点行为

基本信息

批准号：
10245156
负责人：
James Todd Blankenship
金额：
$ 29.49万
依托单位：
UNIVERSITY OF DENVER (COLORADO SEMINARY)
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-20 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10245156
关键词：
Actomyosin Address Adhesions Adult Apical Architecture Area Area Analyses Behavior Biological Biophysics Carcinoma Cell Adhesion Cell Aging Cell physiology Cells Cochlea Communities Complex Contractile Proteins Contracts Coupled Coupling Cytoskeleton Data Development Developmental Process Dimensions Drosophila genus E-Cadherin Embryo Embryonic Development Environment Epithelial Event F-Actin Goals Individual Intention Lead Length Link Maintenance Mechanics Medial Mediating Methods Modeling Molecular Morphogenesis Morphology Movement Myosin Type II Neoplasm Metastasis Organ Organism Palate Phase Physiologic pulse Population Process Protein Analysis Proteins Radial Relaxation Research Resolution Shapes Slide Stretching Structure System Testing Tissues base biophysical analysis biophysical tools cell motility course development intercalation novel novel strategies spatiotemporal tissue repair tool

项目摘要

Project Summary Epithelial sheets sit at the boundary of the organism and its external environment. The maintenance of these apical and basolateral domains is essential to the barrier function of epithelia, and the loss of apical-basal polarity is associated with the metastasis of many epithelial cancers. While epithelial sheets were once viewed as largely static assemblies, it is now appreciated that these are dynamic structures that can undergo significant reorganizing and renewal events. Indeed, cell neighbor exchange can be harnessed by developmental processes to effect changes in tissue architecture, and cell intercalation can drive epithelial tissue repair. In the Drosophila embryonic epithelium, individual cells are able to either consolidate cell-cell contacts or direct neighbor exchange movements through the contraction of vertical T1 interfaces and the subsequent resolution of horizontal T3 interfaces. The dominant model in explaining these behaviors has been one in which line tensions that stretch across interfaces direct these changes. However, a number of observations have led us to question this approach. Our central hypothesis is that cell vertices demonstrate radial coupling and that the best explanation of intercalary behaviors will be through a description of the radially-directed force events that lead to vertex movements and subsequent dependent changes in interface lengths. Our data suggests that tricellular vertices slide along cell- cell interfaces to harness radial forces, and would introduce a new area of research on the molecular and biophysical contributions of cell vertices to embryogenesis. Pulsed oscillations in cell area have been found to drive developmental processes in a number of different systems and tissues, but the mechanisms that link these area oscillations to productive tissue shaping events have been unclear. Because of this, we believe vertex sliding through radial force coupling offers a new, fundamental mechanism that may account for this conservation of oscillatory mechanics. We also will examine the structure and oscillation of adhesion complexes that are located at cell vertices, as well as the relationship between actomyosin forces and changes in vertex structure. We believe the proposed studies will provide a fundamentally new vertex-based mechanism that directs cell intercalation through junctional sliding driven by radial coupling.

项目概要上皮片位于生物体及其外部环境的边界。这维持这些顶端和基底外侧区域对于屏障功能至关重要上皮细胞的变化，顶端-基底极性的丧失与上皮细胞的转移有关许多上皮癌。虽然上皮片曾经被认为基本上是静态的组件，现在人们认识到这些是动态结构，可以经历重大重组和更新事件。事实上，小区邻居交换可以通过发育过程来影响组织结构和细胞的变化嵌入可以驱动上皮组织修复。在果蝇胚胎上皮中，单个细胞能够巩固细胞与细胞的接触或直接相邻通过垂直T1界面的收缩交换运动水平T3接口的后续分辨率。解释中的主导模型这些行为是一种直接跨越界面的线张力的行为这些变化。然而，一些观察结果使我们对此提出质疑方法。我们的中心假设是单元顶点表现出径向耦合并且对闰行为的最佳解释是通过对导致顶点运动和后续依赖的径向力事件接口长度的变化。我们的数据表明，三细胞顶点沿着细胞滑动细胞界面利用径向力，并将引入一个新的研究领域细胞顶点对胚胎发生的分子和生物物理贡献。脉冲式人们发现细胞区域的振荡可以驱动许多发育过程不同的系统和组织，但将这些区域振荡联系起来的机制生产性组织塑造事件尚不清楚。正因为如此，我们相信顶点通过径向力耦合滑动提供了一种新的基本机制，可以解释振荡力学守恒。我们还将检查位于细胞顶点的粘附复合物的结构和振荡作为肌动球蛋白力与顶点结构变化之间的关系。我们相信所提出的研究将提供一种全新的基于顶点的机制通过径向耦合驱动的连接滑动来引导细胞嵌入。