Intercellular Communication and Oocyte Polarity

细胞间通讯和卵母细胞极性

• 批准号: 7671395
• 负责人: Wu-Min Deng
• 金额: $ 24.66万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7671395
• 关键词: Adopted; Adult; Anterior; Back; Cell Communication; Cell Death; Cell Polarity; Cell division; Cell physiology; Cells; Communication; Cytoskeleton; Defect; Development; Developmental Cell Biology; Down-Regulation; Drosophila genus; Dystroglycan; ECM receptor; Embryo; Epidermal Growth Factor Receptor; Extracellular Matrix; Future; Genes; Knowledge; Laminin; Ligands; Mediating; Microtubules; Muscular Dystrophies; Mutation; Notch Signaling Pathway; Oocytes; Oogenesis; Pathway interactions; Play; Process; Protein Tyrosine Phosphatase; Regulation; Research; Research Design; Role; Series; Signal Pathway; Signal Transduction; Specificity; Substrate Interaction; Testing; Time; Work; base; cell motility; cell type; fascinate; fly; human PHEMX protein; insight; intercellular communication; notch protein; novel; receptor

DESCRIPTION (provided by applicant): How polarity is established at a cellular level is one of the most fundamental and fascinating questions in cell and developmental biology. During development, many cell types undergo polarization to adopt forms that are highly adaptable to their specific functions. Disruption of cellular polarity frequently leads to abnormal cellular functions such as cell death, uncontrolled cell division, and irregular cell movement. Cytoskeletons and cell-cell and cell-substrate interactions are known to play important roles in cell polarization, but the mechanisms by which cellular polarity is established, modified, and maintained remain largely unknown. In the research proposed here, we will investigate the regulatory mechanisms through which the developing Drosophila oocyte is polarized. The establishment of the anterior-posterior polarity of the oocyte requires a series of symmetry-breaking steps. A key step that remains unknown is the signaling from the posterior follicle cells to the oocyte at mid- oogenesis, which results in repolarization of the oocyte. Our preliminary studies have revealed that the ECM molecule laminin and its receptor Dystroglycan (DG) are required for proper establishment of oocyte polarity. We propose to analyze the regulation and the role of DG and Laminin in follicle cell-oocyte communication and the mechanism of oocyte polarization. The specific aims are: 1. To establish the regulatory relationship between the EGFR and Notch signaling pathways and DG. 2. To characterize DG- and Laminin-mediated cell-cell communication. 3. To identify and characterize new players involved in follicle cell-oocyte communication and in oocyte polarity formation. This work will advance knowledge of the origin of body axis and the mechanisms by which cell polarity is established and maintained. The project will also provide insights into the novel signaling mechanisms of DG and the Laminin ECM and their roles in cell- cell communication.

描述（由申请人提供）：如何在细胞水平上建立极性是细胞和发育生物学中最基本和最迷人的问题之一。在开发过程中，许多细胞类型经历了极化，以采用高度适应其特定功能的形式。细胞极性的破坏经常导致细胞功能异常，例如细胞死亡，不受控制的细胞分裂和不规则的细胞运动。已知细胞骨架，细胞细胞和细胞基底相互作用在细胞极化中起重要作用，但是建立，修饰和维持的细胞极性的机制仍然很大程度上未知。在此处提出的研究中，我们将研究发育中的果蝇卵母细胞两极分化的调节机制。卵母细胞的前后极性的建立需要一系列对称性的步骤。尚不清楚的关键步骤是在卵子发生时从后卵泡细胞到卵母细胞的信号传导，从而导致卵母细胞复极化。我们的初步研究表明，ECM分子层粘连蛋白及其受体多胶糖（DG）是正确建立卵母细胞极性所必需的。我们建议分析DG和层粘连蛋白在卵泡细胞 - 素环通信中的调节和作用以及卵母细胞极化的机理。具体目的是：1。建立EGFR和Notch信号通路和DG之间的调节关系。 2。表征DG-和层粘连蛋白介导的细胞 - 细胞通信。 3。识别和表征参与卵泡细胞 - 素细胞通信和卵母细胞极性形成的新玩家。这项工作将进一步了解身体轴的起源以及建立和维护细胞极性的机制。该项目还将提供有关DG和层粘连蛋白ECM的新信号传导机制及其在细胞通信中的作用的见解。