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（由申请人提供）：组织和器官的正确功能需要极化细胞。细胞通过各种机制，包括平面细胞极性（PCP）途径，这是该提案的主题。已经表征了PCP途径的许多分子成分，包括上游跨膜FZ受体和下游因子，散乱的，刺，刺，斜视，火烈鸟等。 PCP途径负责产生极化的细胞形态和行为，并在整个组织范围内协调极性。关于PCP途径的许多内容仍然很少了解，包括将PCP机械与细胞结构和功能成分的极化联系起来的机制，以及在全球层面确定组织和器官的极性的机制。该应用建议将剪裁ciona的脊索用作研究PCP途径的模型。双束物是脊椎动物的最接近的现有亲属，但具有较小的基因组，虽然相似，但形态更为相似。这种简单性可在Ciona Notochord中看到，仅由四十个细胞组成。在CIONA NOTOCHORD中，首先是依赖PCP的机制，首先是对中轴/侧轴中细胞的定向插入以形成色谱柱的原因。插入完成时，PCP途径在前轴/后轴上向脊索细胞的第二个极化信号。在第一个特定目标中提出的实验将通过检查核心PCP蛋白定位的时间和空间变化来更充分地表征Ciona notochord的极性，并将解决从中/侧面/后/后极性的过渡以及这两个极性如何链接。第二个特定目的将研究建立全局极性的机制，以及细胞对细胞信号传导在极性传播和维持中的作用。最后，第三个特定目的将尝试揭示作用于中心/前轴和前轴的全局偏振信号的分子身份（IES）。 公共卫生相关性：细胞极性缺陷与许多人类疾病疾病（例如多囊肾脏疾病）有关。该提案将研究基本的细胞极性形成的基本细胞机制。