The germline gives rise to the germ cells of the adult and it thus vitally important for the propagation and survival of a species. It is the only cell type of most cellular organisms whose genetic content contributes to the next generation. Thus maintenance of the integrity of its genome is important for maintaining a species, yet changes in its content also provide a mechanism for change. The long term objective of this application is to gain a molecular understanding of how the germ cell lineage of Drosophila is established during embryogenesis. This proposal focuses on the genetic, molecular and biochemical examination of the germ cell-less gene which is known to be required for the establishment of the germ cell lineage. The germ cell-less gene encodes an mRNA that is localized to the germ plasm which contains the germ cell determinants. Loss of gcl activity in the embryo leads to a failure to form the germ cell precursors and results in sterile individuals. Ectopic placement of gcl results in the ectopic induction of properties found in the germ cell precursors. The germ cell-less gene therefore, plays a central role in the establishment of the germ cell lineage. The goal of this proposal is to determine the biochemical role of the GERM CELL-LESS protein in the process of germ cell specification. A unique property of the germ cell precursors is a period of transcriptional quiescence that is evident as soon as they form and lasts for the first few hours of development. Mutations that disrupt this period of transcriptional quiescence block normal germ line development. Similarly, germ cell precursors formed in gcl mutant embryos inappropriately express genes normally suppressed in wild type embryos and fail to form a germline. In this proposal, we will further characterize transcriptional quiescence in the germ cell precursors and the role that GCL plays in this process. Two proteins, which by homology have predicted roles in transcriptional quiescence, have been found to physically interact with the GERM CELL-LESS protein. In this proposal we will explore the roles of this interaction and the function of these genes with respect to establishing transcriptional quiescence in the germ cell precursors.
| Berkowitz, Karen M; Sowash, Aislinn R; Koenig, Lydia R et al. (2012) Disruption of CHTF18 causes defective meiotic recombination in male mice. PLoS Genet 8:e1002996 |
| Dockendorff, T C; Robertson, S E; Faulkner, D L et al. (2000) Genetic characterization of the 44D-45B region of the Drosophila melanogaster genome based on an F2 lethal screen. Mol Gen Genet 263:137-43 |
| Faulkner, D L; Dockendorff, T C; Jongens, T A (1998) Clonal analysis of cmp44E, which encodes a conserved putative transmembrane protein, indicates a requirement for cell viability in Drosophila. Dev Genet 23:264-74 |
