Intercellular Communication and Polarity

During Drosophila oogenesis, the germline cells and the somatic follicle cells interact constantly, sending signals back and forth to communicate and eventually to build a functional egg for the development of the next generation. These oocytes are asymmetrically constructed, storing positional information, specific mRNAs and proteins that are localized in specific subcellular compartments. When the egg is fertilized, these localized molecules direct the formation of the major body axes—the anterior-posterior (AP) and the dorsal-ventral (DV) axes—a process fundamental to the development of bilateral animals. The localization of these determinants requires the oocyte to build a polarized network of cytoskeleton microtubules. Although many players involved in this polarity formation have been identified, several key steps in the process remain unclear. For example, posterior follicle cells were known to signal a change in oocyte polarity, but the nature of signal remained unknown.

My lab has investigated both the nature of the posterior follicle cell signaling and the responding mechanisms working in the oocyte to establish the proper polarity. We have shown that a follicle-cell extracellular-matrix component is required for proper oocyte polarity. Work in my lab led to the discovery that the Epidermal Growth Factor Receptor signaling pathway, as well as Notch signaling, downregulates expression of Dystroglycan (a transmembrane complex that when defective leads to muscular dystrophy in humans) in follicle cells.

Inside the oocyte, how microtubule polarity is regulated is also largely unclear. Recently, we have revealed a novel pathway that involves tumor-suppressor Lethal Giant Larvae (Lgl) and conserved cell-polarity genes such as aPKC and Par-1 to regulate the microtubule asymmetry in the oocyte.

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Figure 1. Dystroglycan is required in the germline for correct oocyte polarity during early oogenesis (A, B). (A) The wild-type oocyte has enriched actin staining (arrows), but the DG germ-line clone disrupts this enrichment (B). (From Deng et al., 2003).

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