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: 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
• 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

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上。这个 这些顶端和基底外侧结构域的维持对于屏障功能是至关重要的 顶端-基底端极性的丧失与上皮细胞的转移有关。 许多上皮性癌症。虽然上皮片曾经被认为基本上是静态的 组件，现在可以理解的是，这些是动态结构，可以 重大的重组和更新活动。实际上，小区邻居交换可以 利用发育过程来影响组织结构和细胞的变化 插层可以驱动上皮组织修复。在果蝇的胚胎上皮中， 单个单元格能够合并单元格-单元格接触或直接相邻 通过收缩垂直T1接口和 水平T3界面的后续分辨率。解释中的主导模式 在这些行为中，跨界面延伸的线条紧张直接 这些变化。然而，一些观察结果使我们对此提出了质疑 接近。我们的中心假设是单元格的顶点表现出径向耦合 对中间行为的最好解释将是通过对 导致顶点移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，以利用径向力，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 已经发现细胞区域的振荡在许多情况下驱动发育过程 不同的系统和组织，但将这些区域振荡联系起来的机制 富有成效的组织塑造事件一直不清楚。因此，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，它可以 解释了振荡力学的这种守恒性。我们还将研究 位于细胞顶点的黏附复合体的结构和振荡性 因为肌动球蛋白作用力与顶点结构变化之间的关系。我们 我相信拟议的研究将提供一种全新的基于顶点的机制 它通过径向耦合驱动的连接滑动来引导细胞嵌入。