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.
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