Intercellular Communication and Oocyte Polarity

描述(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吸引人的问题之一。在发育过程中，许多类型的细胞会经历极化，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细胞功能的异常，如细胞死亡、细胞分裂失控和细胞运动不规律。细胞骨架、细胞-细胞和细胞-底物相互作用在细胞极化中发挥着重要作用，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。在这里提出的研究中，我们将研究发育中的果蝇卵母细胞极化的调节机制。卵母细胞前后两极的建立需要一系列打破对称性的步骤。一个尚不清楚的关键步骤是在卵子发生中期从后卵泡细胞向卵母细胞发出信号，导致卵母细胞的复极化。我们的初步研究表明，细胞外基质分子层粘连蛋白及其受体dystrolycan(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-卵母细胞通讯中的调节和作用，以及卵母细胞极化的机制。具体目的是：1.建立EGFR和Notch信号通路与DG之间的调控关系。2.研究DG和层粘连蛋白介导的细胞间通讯。3.鉴定和鉴定参与卵泡细胞-卵母细胞通讯和卵母细胞极性形成的新成员。这项工作将促进对体轴的起源以及建立和维持细胞极性的机制的了解。该项目还将深入了解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.