| Popis: |
All multicellular life begins as a single cell—the fertilised egg, from which the adult organism develops. As a general priniciple, as embryos progess through development, changes in cellular status seem to be effected by cell specific transcription factors which regulate specific gene subsets. The SOX (Sry box) family of transcription factors are one such developmentally important class of transcription factors, consisting of twenty mammalian proteins that each contain a single High Mobility Group (HMG) DNA binding domain that is >50% homologous to that of Sry, the mammalian testes determining factor. SOX proteins are multi-functional developmental regulators that sequence specifically bind DNA, and can function both as classical transcription factors and as architectural components of chromatin (Kiefer et al. 2007, Lefebvre et al. 2007). We have been modeling SOX gene function using the Drosophila SOX gene Dichaete (D). D has similar biochemical properties to mammalian SOX proteins, and is essential for embryonic segmentation and cell fate specification (Ma et al. 1998, Russell et al. 1996). In this thesis I detail novel functions of D in oogenesis and adult olfactory system development. Chapter two details D expression and function during oogenesis in Drosophila. We show that D is transiently expressed in the oocyte cytoplasm from region 2 of the germarium through stage 8. We demonstrate that D protein can bind gürken mRNA, which was mislocalised in D mutant egg chambers. These studies contribute to our understanding of the establishment of dorsal/ventral polarity and significantly detail a cytoplasmic role for SOX proteins in binding mRNA (Mukherjee et al., 2006). Chapter three details the expression and function of D in the adult Drosophila nervous system. I show that D is prominently expressed in a mixture of excitatory and inhibitory local neurons (LNs) and central complex ring neurons. Hypomorphic D alleles were generated, and the mutant brains exhibited misplacement and mistargeting of specific olfactory projection neurons. These data greatly enhance our understanding of the development of neuronal connectivity in a discrete neural map represented by the fly antennal lobe, and represent a detailed report of SOX gene expression in the adult brain. |
