Dynamics of vertebrate planar cell polarity proteins

脊椎动物平面细胞极性蛋白的动力学

• 批准号: 8986583
• 负责人: John B Wallingford
• 金额: $ 18.77万
• 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 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8986583
• 关键词: Adopted; Animal Model; Animals; Behavior; Behavior Control; Biological Models; Cells; Chimeric Proteins; Cilia; Communities; Data; Development; Developmental Biology; Disease; Drosophila genus; Drosophila inturned protein; Dsh protein; Epithelium; Foundations; Funding; Future; Genes; Genetic; Goals; Homeostasis; Human; Hydrocephalus; Image; Image Analysis; Individual; Insecta; Life; Limb structure; Link; Mammals; Microscopy; Modeling; Mutation; Neural Tube Defects; Organ; Pathology; Pattern; Property; Protein Dynamics; Proteins; Reporter; Reporting; Research; Resolution; Resources; Side; Signal Pathway; Signal Transduction; Structural Congenital Anomalies; System; Time; Tissues; Transgenic Organisms; United States National Institutes of Health; Xenopus; body system; cell behavior; cell cortex; fluid flow; in vivo; in vivo imaging; insight; malignant breast neoplasm; novel; planar cell polarity; polarized cell; protein complex; public health relevance; research study; respiratory; time use; tool; vector

 DESCRIPTION (provided by applicant): The Planar Cell Polarity (PCP) signaling system is an evolutionarily conserved genetic module that controls polarized cell behavior in animals and is broadly essential for vertebrate development. Among the many behaviors controlled by PCP signaling is the oriented beating of motile cilia, which is central to generating the fluid flow tht is crucial for homeostasis and function in many organ systems, including the airway. Despite the fact that mutation of PCP genes in humans is associated with diverse structural birth defects, studies of PCP protein dynamics have been largely limited to Drosophila, which unlike mammals is highly amenable to live imaging. The immediate goal of this proposal is to develop and exploit novel tools for exploring the dynamics of PCP proteins via live imaging in a vertebrate ciliated epithelium. Understanding the mechanisms of PCP function is an important challenge in developmental biology, and this proposal will generate new, easily adopted tools for the community. Moreover, the proposed experiments will substantially advance our understanding of vertebrate-specific mechanisms of PCP signaling, providing insights into human structural birth defects such as neural tube defects and congenital limb anomalies.

 描述(申请人提供)：平面细胞极性(PCP)信号系统是一个进化保守的遗传模块，控制动物的极化细胞行为，对脊椎动物的发育非常重要。在PCP信号控制的许多行为中，运动纤毛的定向跳动是产生液体流动的核心，对包括呼吸道在内的许多器官系统的动态平衡和功能至关重要。尽管人类PCP基因的突变与各种结构性出生缺陷有关，但对PCP蛋白动力学的研究在很大程度上局限于果蝇，因为与哺乳动物不同，果蝇非常适合活体成像。这项提议的直接目标是开发和开发新的工具，通过在脊椎动物纤毛上皮中进行实时成像来探索PCP蛋白的动态。了解PCP的作用机制是发育生物学中的一个重要挑战，这一提议将为社区产生新的、易于采用的工具。此外，拟议的实验将极大地促进我们对脊椎动物特有的PCP信号机制的理解，为人类结构性出生缺陷提供见解，如神经管缺陷和先天性肢体畸形。