RNA LOCALIZATION AND TRANSLATIONAL REGULATION DURING DEVELOPMENT IN DROSOPHILA
Localization of proteins to particular regions of cells or tissues is fundamental to the generation of asymmetry during development and the polarization of differentiated cells like neurons. In many cell types, protein synthesis can be targeted to sites where proteins are needed through the localization of their mRNAs. Furthermore, coupling of mRNA localization to translational control restricts protein synthesis to the target destination. Our lab studies the cellular and biochemical mechanisms of mRNA localization and localization-dependent translational control during oogenesis, embryogenesis, and neural development in Drosophila melanogaster.
We focus largely on two mRNAs, bicoid and nanos, whose localization to opposite ends of the Drosophila oocyte provides the sources for protein gradients that pattern the anterior-posterior body axis of the embryo. We have adapted a system for fluorescently tagging mRNAs in vivo to Drosophila and have used this system to visualize movement of bicoid and nanos; mRNAs in living oocytes. In vivo imaging has also facilitated dissection of the very different localization pathways used by these two mRNAs. At the molecular level, we have identified a complex cis-acting RNA localization signal that directs nanos to the posterior of the oocyte, where its translation is activated. Using genetic and biochemical approaches, we have begun to identify factors that recognize this signal and help to package nanos for transport. Unlocalized nanos mRNA is translationally repressed by a cis-acting translational control element (TCE) that interacts with an ovarian repressor, Glorund, and an ovarian repressor, Smaug. We are currently investigating how Smaug and Glorund regulate nanos differentially during oogenesis and embryogenesis. A recently discovered role fornanos in dendrite morphogenesis has led us to investigate its regulation in neurons as well.