Germ Cell Differentiation and mRNA Translation Programs

Stained drosophila ovary
 Germarium stained for Vasa (blue), Hts (red), and Rbfox1 (green).

Post-transcriptional gene regulation has emerged as a critical control mechanism that orchestrates diverse cellular processes during germ cell differentiation. We have extensive preliminary data that demonstrate cytoplasmic Rbfox1 represses the translation of specific target mRNAs that contain (U)GCAUG elements within their 3’ untranslated regions during specific stages of germline-cyst differentiation.

Moving forward, we seek to characterize the detailed mechanisms by which cytoplasmic Rbfox1 regulates stage-specific mRNA translation programs during germ-cell cyst development. Our general strategy is to:

  • Characterize how Rbfox1 regulates specific mRNAs—such as pumilio and sex-lethal—that govern early steps of germ cell development, and determine how ectopic expression of these targets contributes to Rbfox1-mutant phenotypes.
  • Determine what mechanisms control the unique protein expression pattern of Rbfox1 during the intermediate stages of germline-cyst differentiation, prior to the onset of meiosis.
  • Characterize how Rbfox1 molecularly regulates the translation of mRNA targets to achieve stage-specific translational repression.

We anticipate that these efforts will provide key insights into the translational control hierarchies that promote the development of germ cells across species.