I have investigated the mechanisms by which developmental asymmetry arises, using oocyte determination in Drosophila melanogaster as a model system. The Bicaudal-D (Bic-D) gene is required early in oogenesis for the asymmetric localization of specific mRNAs and proteins and for the differentiation of an oocyte from one of a cluster of 16 interconnected germarial cells. To better understand how Bic-D functions in creating this asymmetry, I took two approaches. First, I examined the role of Bic-D in the asymmetric localization of mRNA and other cellular components during later oogenesis. Second, I molecularly and genetically characterized a gene that interacts with Bic-D in oocyte determination. To determine the role of Bic-D in later oogenesis, I used an inducible source of Bic-D activity to selectively rescue the block at oocyte determination in Bic-D null mutants. Using this system, I find that Bic-D is indeed required in the later stages of oogenesis for the localization of specific mRNAs at both the anterior and posterior of the oocyte. Bic-D is also required for oocyte growth and nuclear positioning, processes which also depend on microtubules. / In the second part of this thesis, I describe the characterization of a Bic-D interacting gene which I have identified as the Drosophila homologue of the human Lissencephaly-1 (Lis-1) gene, DLis-1. Human Lis-1 is the causative gene for Miller-Dieker Syndrome and is required for neuronal migration in the developing brain, while fungal homologues have been implicated in dynein dependent nuclear migration. Like Bic-D , DLis-1 is essential for oocyte determination and for intracellular localization throughout oogenesis. DLis-1 is required for correct positioning of the oocyte nucleus, and appears to function upstream of dynein in this process. Immunolocalization studies suggest that DLis-1 functions as part of a cortical anchor that links microtubules and the oocyte nucleus, via dynein and microtubules, to the cell cortex. DLis-1 and Bic-D are also required for nuclear positioning during neural development in Drosophila, supporting a model in which the neuronal migration defects in Miller-Dieker Syndrome are due to a disruption of dynein/Lis-1 dependent nuclear migration.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.36063 |
| Date | January 1999 |
| Creators | Swan, Andrew. |
| Contributors | Suter, Beat (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Biology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001797599, proquestno: NQ55384, Theses scanned by UMI/ProQuest. |
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