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

• 批准号: 9789335
• 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
• 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/9789335
• 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; Epithelium; 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

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.

项目摘要 上皮层位于生物体及其外部环境的边界。的 这些顶侧和基底侧区域的维持对于屏障功能至关重要 的上皮细胞，和顶部-基底极性的损失与转移相关的 许多上皮癌。虽然上皮层曾经被视为基本上是静态的， 尽管本领域技术人员将认识到这些组件是动态结构， 重大重组和更新事件。实际上，小区邻居交换可以是 通过发育过程来影响组织结构和细胞 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-细胞接触或直接相邻细胞 通过垂直T1界面的收缩和 水平T3界面的后续分辨率。解释这一现象的主导模型 这些行为是一种跨越界面的线张力直接 这些变化。然而，一些观察结果使我们对此提出质疑 approach.我们的中心假设是细胞顶点表现出径向耦合， 对插入行为的最好解释是通过描述 导致顶点移动的径向力事件和随后的依赖 界面长度的变化。我们的数据表明三细胞顶点沿着细胞- 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 已经发现细胞面积的振荡驱动许多细胞的发育过程， 不同的系统和组织，但是将这些区域振荡与 生产性组织成形事件尚不清楚。因此，我们认为顶点 通过径向力耦合的滑动提供了一种新的基本机构，其可以 来解释振荡力学的守恒。我们还将研究 位于细胞顶点的粘附复合物的结构和振荡，以及 肌动球蛋白力和顶点结构变化之间的关系。我们 我相信，拟议中的研究将提供一种全新的基于顶点的机制 其通过由径向耦合驱动的接合滑动来引导细胞嵌入。