Intercellular Communication and Oocyte Polarity

描述（由申请人提供）：极性如何在细胞水平上建立是细胞和发育生物学中最基本和最吸引人的问题之一。在发育过程中，许多细胞类型经历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异常的细胞功能，例如细胞死亡、不受控制的细胞分裂和不规则的细胞运动。已知细胞骨架和细胞-细胞和细胞-基质相互作用在细胞极化中起重要作用，但细胞极性建立、修饰和维持的机制在很大程度上仍不清楚。在本研究中，我们将探讨果蝇卵母细胞极化的调控机制。卵母细胞前-后极性的建立需要一系列的破卵步骤。一个关键的步骤，仍然是未知的，是信号从后卵泡细胞卵母细胞在中期卵子发生，这导致复极的卵母细胞。我们的初步研究表明，ECM分子层粘连蛋白及其受体Dystroglycan（DG）是卵母细胞极性正确建立所必需的。本文拟从DG和Laminin在卵泡细胞-卵母细胞通讯中的调控和作用以及卵母细胞极化的机制等方面进行分析。具体目标是：1.建立EGFR和Notch信号通路与DG的调控关系。2.表征DG和层粘连蛋白介导的细胞间通讯。3.识别和表征参与卵泡细胞-卵母细胞通讯和卵母细胞极性形成的新参与者。这项工作将推进身体轴的起源和细胞极性建立和维持的机制的知识。该项目还将提供深入了解DG和层粘连蛋白ECM的新信号机制及其在细胞间通讯中的作用。

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.