The aim of this thesis was the analysis of the role of nucleocytoplasmic transport factors in <i>Drosophila </i>development. Potential nucleocytoplasmic transport factors in <i>Drosophila</i> were identified in database searches by their homology to known factors from yeast and humans. For candidate factors the sequence and mRNA expression pattern was further analysed. While most mRNAs tested were ubiquitously expressed, one newly identified factor, called <i>Drosophila</i> <i>cas </i>(<i>dcas</i>), because of its homology to human CAS (cellular apoptosis susceptibility factor), showed a specific expression pattern, Zygotic <i>dcas</i> mRNA was highly enriched in the embryonic central nervous system, although the protein showed a generalised distribution. Mutations in <i>dcas</i> were identified and analysed. A P-element insertion in the <i>dcas</i> gene causes lethality, whereas several hypomorphic alleles showed specific phenotypes at different developmental stages. Detailed analysis revealed that Dcas functions in the export of importin-α in <i>Drosophila, </i>as previously reported for humans and yeast. However, mutations in <i>dcas </i>also resulted in highly specific defects fate determination in the peripheral nervous system during the development of the external sensory organ (commonly known as “bristles”). Similar phenotypes have been reported in mutants that increase signalling by the Notch pathway. Several components of this pathway were therefore tested for localisation defects in <i>dcas </i>mutants and one protein showed an altered nuclear/cytoplasmic distribution. These findings confirm that Dcas has the same basic function in the export of importin-α in intact <i>Drosophila </i>as in single cells of humans and yeast. In addition to this “house-keeping” function, mutations in <i>dcas</i> cause specific phenotypes, indicating that some pathways are particularly sensitive to a perturbation in nuclear protein important. This is very likely applicable to other transport factors in other multicellular organisms.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:662803 |
| Date | January 2002 |
| Creators | Tekotte, Hildegard |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/13099 |
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