Deciphering molecular mechanisms that regulate programmed cell death of primordial germ cells in Drosophila melanogaster

Abstract

<p>Programmed cell death (PCD) is a genetically regulated process that is central to life of multicellular organisms. During development, PCD serves to sculpt tissues, remove temporary structures, regulate cell populations, and eliminate harmful cells. Deregulation of PCD can lead to medical conditions such as cancer and neurodegenerative disorders. Core components of PCD machineries are conserved across the animal phyla. Therefore, studies in model organisms provide valuable insights for further understanding of this very important process. The research presented here uses Drosophila primordial germ cells as a model system to investigate genes that are important for germ cell PCD. During embryogenesis, approximately 50% of germ cells that initially form are efficiently eliminated via PCD. However, mechanisms by which germ cells undergo PCD remain unknown. We have identified the outsiders (out) gene is essential for germ cell PCD. Initial characterization of out mutants revealed that out is required zygotically for germ cell PCD. out is predicated to encode a monocarboxylate transporter. In addition, genetic approaches were taken to investigate involvement of other known cell death regulators in germ cell PCD and their possible interactions with out. We examined the two prominent PCD machineries, apoptosis and autophagy, in germ cell PCD. Our observations showed that germ cell death in wild-type embryos is independent of potent pro-apoptotic genes, grim, reaper, hid, and caspase Dronc. Studies of several autophagy mutants did not result in severe germ cell phenotype. Our observations suggest that blocking one mode of PCD may not be enough to stop germ cell elimination. These findings have allowed elucidating of more accurate molecular model for germ cell PCD.</p>