Control of collective cell movement by planar cell polarity signaling

通过平面细胞极性信号控制集体细胞运动

基本信息

批准号：
9127983
负责人：
John B Wallingford
金额：
$ 31.68万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9127983
关键词：
Actins Actomyosin Address Anencephaly and spina bifida X linked Area Automobile Driving Behavior Biochemical Biological Assay Biology Cell Shape Cells Communication Conflict (Psychology)Congenital Abnormality Data Defect Development Dissection Drosophila genus Failure Gap Junctions Gastrula Gene Family Genes Health Human Image Intercellular Junctions Knowledge Lasers Life Light Link Mediating Microdissection Molecular Morphogenesis Motor Movement Mutation Myosin ATPase Myosin Type II Neural Tube Closure Neural Tube Defects Pattern Polycystic Kidney Diseases Process Protein Dynamics Proteins Renal tubule structure Reporter Reporting Role Set protein Signal Transduction Spinal Dysraphism Study models Surveys System Time Traction Vertebrates Work cell behavior cell cortex cell motility convergent extension fly gastrulation insight intercalation novel planar cell polarity polarized cell protein function research study

项目摘要

DESCRIPTION (provided by applicant): The Planar Cell Polarity (PCP) proteins are a highly conserved molecular system for coordinating cells within a sheet, and in vertebrate animals, these proteins control collective cell movements termed convergent extension. This proposal seeks to address two key outstanding issues in vertebrate PCP biology. 1) Actomyosin contraction is the key driver of most cell movements, but surprisingly little is yet known about th links between PCP proteins and actomyosin contraction, especially in vertebrates. We will determine the role of PCP proteins in controlling the spatial and temporal patterns of Myosin II activation in cells engaged in convergent extension. We will combine live imaging approaches and laser-microdissection to investigate cell shape changes, dynamic protein localization, and cell cortex tension during convergent extension. 2) The dynamic localization of PCP proteins is central to their normal function, but how these proteins are localized during convergent extension and how their localization drives collective cell movements in unknown. We will use live imaging new fluorescent reporters to address this issue during vertebrate gastrulation. Impact: PCP-mediated convergent extension is essential for neural tube closure, and mutations in PCP genes can be causative for human birth defects that result from failure of neural tube closure. The experiments proposed here will thus inform our understanding human neural tube defects such as spina bifida. In addition, recent data now suggest a role for PCP-dependent convergent extension in the morphogenesis of kidney tubules, so experiments proposed here will shed new light on mechanisms underlying congenital polycystic kidney disease.

描述（由适用提供）：平面细胞极性（PCP）蛋白是一种高度保守的分子系统，用于薄板内的协调细胞，在脊椎动物动物中，这些蛋白质控制的集体细胞运动称为收敛延伸。该建议旨在解决脊椎动物PCP生物学中的两个关键问题。 1）肌动蛋白收缩是大多数细胞运动的关键驱动力，但是对于PCP蛋白与肌动蛋白收缩之间的TH连接，尤其是在脊椎动物中，仍然很少知道。我们将确定PCP蛋白在控制收敛延伸的细胞中肌球蛋白II激活的空间和临时模式中的作用。我们将结合实时成像方法和激光 - 显微解次切除术，以研究收敛延伸过程中细胞形状的变化，动态蛋白质定位和细胞皮质张力。 2）PCP蛋白的动态定位是其正常功能的核心，但是这些蛋白如何在收敛扩展过程中定位，以及它们的定位如何驱动未知的集体细胞运动。我们将使用现场成像新的荧光记者在脊椎动物胃胃期间解决此问题。影响：PCP介导的收敛延伸对于神经管闭合至关重要，而PCP基因的突变对于由于神经元管闭合失败而导致的人类出生缺陷可能是严重的。因此，这里提出的实验将为我们理解人类中性管缺陷，例如脊柱裂。此外，最近的数据现在表明，依赖PCP依赖性的收敛扩展在肾管的形态发生中起作用，因此，此处提出的实验将为先天性多囊肾脏病的机制提供新的启示。