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Title: The role of the exportin CAS during peripheral nervous system development in Drosophila melanogaster
Author: Tekotte, Hildegard
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2002
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The aim of this thesis was the analysis of the role of nucleocytoplasmic transport factors in Drosophila development. Potential nucleocytoplasmic transport factors in Drosophila 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 Drosophila cas (dcas), because of its homology to human CAS (cellular apoptosis susceptibility factor), showed a specific expression pattern, Zygotic dcas mRNA was highly enriched in the embryonic central nervous system, although the protein showed a generalised distribution.  Mutations in dcas were identified and analysed. A P-element insertion in the dcas 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 Drosophila, as previously reported for humans and yeast. However, mutations in dcas 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 dcas 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 Drosophila as in single cells of humans and yeast. In addition to this “house-keeping” function, mutations in dcas 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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available