Robert Boswell - Professor

Cell-cell interactions are important for establishing cellular diversity during the development of multicellular organisms. In the fruitfly Drosophila melanogaster, inductive interactions between the germline-derived oocyte and the overlying somatic posterior follicle cells are crucial for the defining the axes of the oocyte. Proper formation of the axes during oogenesis is also important for delineation of the major body axes of the embryo and adult. In addition, posterior follicle cell-to-oocyte signaling results in the accumulation of specific proteins and RNAs within a specialized region of cytoplasm at the posterior of the oocyte. The proteins and RNAs localized within this subcellular compartment are indispensable for the differentiation of germ cells and abdominal segmentation of the embryo. Thus, the posterior pole cytoplasm has been designated as germ plasm. Although these inductive interactions are critical for defining the axes and determination of the germline, thus far, few components that function within the oocyte to regulate this important signal transduction pathway have been identified. Our strategy is to use genetic and molecular techniques to identify and characterize genes essential for delineating the body axes and germ cell determination in Drosophila.

Our genetic and molecular analyses of mago nashi (mago) indicate that the mago gene encodes one such factor.The mago+ function is required within the oocyte to regulate the response of the oocyte to the posterior follicle cell signal. Furthermore, Mago protein must be localized within the posterior pole for the assembly of components necessary for germ cell formation. Utilizing a yeast two-hybrid screen, we identified Tsunagi protein as a Mago interactor. Tsunagi is an RNA-binding protein that forms a complex with Mago. The complex functions to establish the major body axes in response to the follicle cell signal and is also indispensable for assembly of germ plasm components. Experiments currently underway in the laboratory are designed with the following objectives: (a) gaining further insights into the roles of mago and tsunagi in oogenesis; and (b) identifying proteins and RNAs that interact with the Mago:Tsunagi complex to regulate axis formation and germ plasm assembly. Our long-term goals are to elucidate the molecular mechanisms involved in defining the major body axis and assembly of germ plasm components. Mago and Tsunagi are highly conserved in flies and humans, suggesting that an understanding of how the fly proteins function in axis formation and germ cell determination will reveal their developmental roles in localizing components important for similar developmental processes in vertebrates.