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

• 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
• 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

 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(申请人提供)：平面细胞极性(PCP)蛋白是一种高度保守的分子系统，用于协调片状细胞，在脊椎动物中，这些蛋白控制称为收敛延伸的集体细胞运动。这项提议旨在解决脊椎动物PCP生物学中的两个关键悬而未决的问题。1)肌动球蛋白收缩是大多数细胞运动的关键驱动力，但令人惊讶的是，对于PCP蛋白和肌动球蛋白收缩之间的联系，尤其是在脊椎动物中，人们知之甚少。我们将确定PCP蛋白在控制参与汇聚延伸的细胞中肌球蛋白II激活的空间和时间模式中的作用。我们将结合实时成像方法和激光显微解剖来研究融合延伸过程中细胞形状的变化、蛋白质的动态定位以及细胞皮质的张力。2)PCP蛋白的动态定位是其正常功能的核心，但这些蛋白在融合延伸过程中是如何定位的，以及它们的定位如何驱动集体细胞的运动是未知的。我们将使用实时成像新的荧光记者来解决脊椎动物原肠发育过程中的这个问题。影响：PCP介导的会聚延伸是神经管闭合的关键，PCP基因的突变可能导致因神经管闭合失败而导致的人类出生缺陷。因此，这里提出的实验将使我们了解人类神经管缺陷，如脊柱裂。此外，最近的数据表明PCP依赖的会聚延伸在肾小管的形态发生中起作用，因此这里提出的实验将为先天性多囊肾病的发病机制提供新的线索。