Exploring Planar Cell Polarity in A Novel Invertebrate Chordate System

探索新型无脊椎动物脊索系统中的平面细胞极性

• 批准号: 8307006
• 负责人: William Smith
• 金额: $ 27.13万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8307006
• 关键词: Ablation; Address; Anterior; Biological Assay; Biological Models; Cell Communication; Cell Nucleus; Cell Polarity; Cells; Cellular Morphology; Cellular Structures; Chordata; Cochlea; Core Protein; Defect; Embryo; Embryonic Development; FGF3 gene; Fatty acid glycerol esters; Gastrula; Genes; Genome; Goals; Invertebrates; Kidney; Lasers; Lateral; Lesion; Link; Maintenance; Modeling; Molecular; Morphogenesis; Morphology; Nature; Neural tube; Neurula; Organ; Pathway interactions; Polycystic Kidney Diseases; Process; Property; Proteins; Publishing; Relative (related person); Role; Side; Signal Pathway; Signal Transduction; Staging; Strabismus; System; Testing; Time; Tissues; Urochordata; Vertebrates; Work; ascidian; cell behavior; human disease; intercalation; mutant; notochord; novel; polarized cell; public health relevance; receptor; research study; response

DESCRIPTION (provided by applicant): The proper functioning of tissues and organs requires polarized cells. Cells acquire polarized morphologies (i.e., differences in subcellular composition from one side of the cell to the other) through various mechanisms, including the planar cell polarity (PCP) pathway, which is the subject of this proposal. A number of molecular components of the PCP pathway have been characterized, including the upstream transmembrane Fz receptor and the downstream factors, disheveled, prickle, strabismus, flamingo, and others. The PCP pathway is responsible for generating polarized cell morphologies and behaviors, and for coordinating polarity on a tissue-wide scale. Much about the PCP pathway remains poorly understood, including the mechanisms that link PCP machinery to polarization of structural and functional components of the cell, and the mechanism by which the polarity of tissues and organs is determined at a global level. This application proposes to use the notochord of the tunicate Ciona as a model to study the PCP pathway. Tunicates are the closest extant relatives of vertebrates, but have much smaller genomes, and simpler, though similar, morphology. This simplicity is seen in the Ciona notochord which consists of only forty cells. In the Ciona notochord, PCP-dependant mechanisms are responsible, first, for the directed intercalation of cells in the medio/lateral axis to form a column. At the completion of intercalation, the PCP pathway signals a second polarization of the notochord cells, this time in the anterior/posterior axis. Experiments proposed in the first specific aim will more fully characterize Ciona notochord polarity by examining the temporal and spatial changes in core PCP protein localization, and will address the transition from medio/lateral to anterior/posterior polarity and how these two polarities are linked. The second specific aim will investigate mechanisms by which global polarity is established and the role of cell-to-cell signaling in propagation and maintenance of polarity. Finally, the third specific aim will attempt to uncover the molecular identity(ies) of the global polarizing signals acting both in the medio/lateral and anterior/posterior axes. PUBLIC HEALTH RELEVANCE: Defects in cell polarity are associated with many human disease conditions, such as polycystic kidney disease. The proposal will investigate the fundamental cellular mechanism that underlies the formation of cell polarities.

描述(申请人提供)：组织和器官的正常功能需要极化的细胞。细胞通过各种机制获得极化形态(即细胞一侧到另一侧的亚细胞组成的差异)，包括平面细胞极性(PCP)途径，这是本提议的主题。PCP途径的许多分子组成已被鉴定，包括上游跨膜FZ受体和下游因子、蓬乱、刺痛、斜视、火烈鸟等。PCP途径负责产生极化的细胞形态和行为，并在组织范围内协调极性。关于PCP途径的许多方面仍然知之甚少，包括将PCP机制与细胞结构和功能组件的极化联系起来的机制，以及在全球水平上决定组织和器官的极性的机制。本申请提出以被膜脊索作为研究PCP途径的模型。被囊动物是现存脊椎动物最近的近亲，但基因组要小得多，形态也更简单，尽管相似。这种简单性体现在只有40个细胞的脊索上。在Ciona脊索中，PCP依赖的机制首先负责细胞在中轴/侧轴的定向插入形成柱状。在插入完成时，PCP通路发出脊索细胞第二极化的信号，这次是在前轴/后轴。第一个具体目标中提出的实验将通过研究核心PCP蛋白定位的时间和空间变化来更全面地表征Ciona脊索极性，并将解决从中间/侧向到前/后极性的转换以及这两个极性是如何联系的。第二个具体目标将研究建立全球极性的机制，以及细胞间信号在传播和维持极性中的作用。最后，第三个具体目标将试图揭示作用于中轴/侧轴和前轴/后轴的全球极化信号的分子同一性。 公共卫生相关性：细胞极性缺陷与许多人类疾病有关，如多囊肾病。该提案将研究细胞极性形成的基本细胞机制。