Germ cells are essential for the maintenance of all sexually reproducing species. Many cellular and molecular aspects of germ cell behavior including their early development as primordial germ cells (PGCs) and their differentiation into sperm and egg are conserved throughout the animal kingdom. This proposal focuses on the analysis of PGC migration. In most organisms PGCs originate at one place of the early embryo and migrate through the embryos to reach the somatic part of the gonad, where they differentiate. This process is intricately regulated and failures in embryonic germ cell migration have been attributed to the origin of extragonadal germ cell tumors in humans. This proposal combines biochemical and genetic approaches with in vivo imaging analysis to understand how migratory cues are integrated overtime and space using Drosophila as a model. In vivo imaging will be used to follow the germ cell migratory path during their transepithelial migration through the posterior midgut and their subsequent homing towards the somatic gonad in wild type and mutants. The G protein coupled receptor (GPCR), Tre-1, will be analyzed with regard to its role in initiating the migratory program and in transepithelial migration. The molecular nature of attractant and repellant somatic guidance cues will be characterized by studying the function of the previously identified lipid phosphatase pathway that is controlled, by Wunen and Wunen2, two homologs of mammalian lipidphosphate phosphatase 3, and by analyzing the isoprenoid pathway, that is controlled by HMGCoA reductase. With a more detailed knowledge of the pathways involved, the interplay between GPCR and Wunen function in germ cells, and the integration of somatic signaling by the Wunen and HMGCoA reductase pathways in the soma will be addressed. The overall goals of this proposal are to connect the molecular network of germ cell migration with the cellular parameters of the developing embryo. Aspects of germ cell migratory behavior are shared with other solitary migrating cells, such as cell of the immune system and metastasizing cancer cells. Thus, the analysis of the genetically easily amenable fruit fly germ cell system is likely to reveal more general principles controlling cell migration.
| Pae, Juhee; Cinalli, Ryan M; Marzio, Antonio et al. (2017) GCL and CUL3 Control the Switch between Cell Lineages by Mediating Localized Degradation of an RTK. Dev Cell 42:130-142.e7 |
| Slaidina, Maija; Lehmann, Ruth (2017) Quantitative Differences in a Single Maternal Factor Determine Survival Probabilities among Drosophila Germ Cells. Curr Biol 27:291-297 |
| Lehmann, Ruth (2016) Germ Plasm Biogenesis--An Oskar-Centric Perspective. Curr Top Dev Biol 116:679-707 |
| Sanchez, Carlos G; Teixeira, Felipe Karam; Czech, Benjamin et al. (2016) Regulation of Ribosome Biogenesis and Protein Synthesis Controls Germline Stem Cell Differentiation. Cell Stem Cell 18:276-90 |
| Hurd, Thomas Ryan; Herrmann, Beate; Sauerwald, Julia et al. (2016) Long Oskar Controls Mitochondrial Inheritance in Drosophila melanogaster. Dev Cell 39:560-571 |
| Hurd, Thomas R; Sanchez, Carlos G; Teixeira, Felipe K et al. (2015) Ultrastructural Analysis of Drosophila Ovaries by Electron Microscopy. Methods Mol Biol 1328:151-62 |
| Malone, Colin D; Lehmann, Ruth; Teixeira, Felipe Karam (2015) The cellular basis of hybrid dysgenesis and Stellate regulation in Drosophila. Curr Opin Genet Dev 34:88-94 |
| Teixeira, Felipe K; Sanchez, Carlos G; Hurd, Thomas R et al. (2015) ATP synthase promotes germ cell differentiation independent of oxidative phosphorylation. Nat Cell Biol 17:689-96 |
| Slaidina, Maija; Lehmann, Ruth (2014) Translational control in germline stem cell development. J Cell Biol 207:13-21 |
| Hurd, Thomas Ryan; Leblanc, Michelle Gail; Jones, Leonard Nathaniel et al. (2013) Genetic modifier screens to identify components of a redox-regulated cell adhesion and migration pathway. Methods Enzymol 528:197-215 |
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