权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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.

项目总结