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An investigation into novel molecules involved in the development of the nervous system of Drosophila melanogaster

An investigation into novel molecules involved in the development of the nervous system of Drosophila melanogaster

Robinson, David (2015) An investigation into novel molecules involved in the development of the nervous system of Drosophila melanogaster. PhD thesis, University of Greenwich.

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A major facet of nervous system development entails the projection of axons from neuronal cell bodies towards synaptic partners, such as other neurons or muscles. This process, referred to as “axon guidance,” relies upon receptors on axons detecting secreted or membrane-associated guidance cues within the developing organism, which attract or repel axons. While many cues and receptors have been identified over the last few decades, many within studies of the relatively simple fly embryonic nervous system, bioinformatic analyses of the Drosophila proteome suggest numerous uncharacterised proteins might be implicated in directing axonal growth. Such proteins are predicted to be expressed at the cell membrane, to harbour domains common to established axon guidance proteins, and to be expressed in the nervous system while axons are extending. The current study focuses on three genes predicted to encode proteins with the above characteristics: CG7565, CG31814, and otk2. An examination of a line with a P-element in the coding sequence of CG7565 revealed aberrations throughout the embryonic motor neurons. Abnormalities in these nerves were also observed in a line with a deficiency spanning CG7565, as well as in embryos misexpressing CG7565 in motor neurons or somatic muscle. Motor neuron projections were absent in embryos harbouring a P-element in the 5’ UTR of CG31814, which were rescued by the precise excision of the transposon. In null otk2 mutant embryos, various motor axons were absent or abnormal, and aberrations in the same branches were apparent when misexpressing otk2 in motor neurons or somatic muscle. Moreover, analyses of transheterozygous embryos provide evidence that otk2 genetically interacts with the established axon guidance genes, otk, sema-1a, and fz2, and that otk interacts with fz2. Analysis of a line with a deficiency that removes otk and otk2 revealed more severe phenotypes than were observed in single mutants, providing further support for cooperation between the off-tracks. Thus, taken together these observations implicate three largely uncharacterised genes in axon guidance and reveal novel insights into the signalling pathways in which these and established axon guidance genes participate.

Item Type: Thesis (PhD)
Uncontrolled Keywords: biology, Drosophila melanogaster,
Subjects: Q Science > QH Natural history > QH301 Biology
Faculty / Department / Research Group: Faculty of Engineering & Science
Faculty of Engineering & Science > School of Science (SCI)
Last Modified: 15 Nov 2017 14:26
Selected for GREAT 2016: None
Selected for GREAT 2017: None
Selected for GREAT 2018: None
Selected for GREAT 2019: None
Selected for REF2021: None

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