‘Investigating the regulation of growth by nitric oxide signalling in Drosophila melanogaster’

Khosravi, Mona (2012) ‘Investigating the regulation of growth by nitric oxide signalling in Drosophila melanogaster’. Doctoral thesis (DPhil), University of Sussex.

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Abstract

Mechanisms associated with growth regulation have been shown to be highly conserved in mammals and Drosophila, especially when examining the insulin signalling pathway. Previous studies suggest that nitric oxide (NO) signalling can inhibit growth and cell proliferation in a Drosophila forkhead box O (dFOXO)- dependent manner. dFOXO is a component of the insulin signalling pathway and has also been demonstrated to inhibit growth via its interactions with components in this pathway; however, the mechanism by which dFOXO and NO interact is unclear.

Since inhibition of growth by NO is dependent on dFOXO, this thesis examines the effect of co-expressing nitric oxide synthase II (NOS2) with three dFOXO alleles (dFOXO25, dFOXO21 and dFOXOBG01018) in Drosophila salivary glands taken from third instar larvae. It concludes that the dFOXO25 null allele appeared to be the strongest deletion of dFOXO given that salivary gland nuclei appear most similar in size to the wild type. This indicates that NO-induced growth inhibition only occurred to a very small degree as a result of a powerful loss-of-function of dFOXO exhibited in dFOXO25 homozygotes.

This thesis also investigates the effects of NO on salivary glands taken from the same developmental stage when co-expressed with overexpressed oncogenes, dMyc and RasV12. Nuclei measurements were larger than the NOS2-only expressing line and smaller than the lines expressing only each of the oncogenes. However, TEM analysis revealed that co-expression might induce endoplasmic reticulum (ER) stress in the glands. Research shows that NO and these oncogenes can provide the reactants necessary to generate peroxynitrite, which is associated with the generation of ER stress.

When examining the effects of these growth regulators on mitochondria and Golgi, this thesis reports that dFOXO, NOS2 and dMyc can increase mitochondrial biogenesis. Golgi was unaffected by expression of the growth regulators

Item Type: Thesis (Doctoral)
Schools and Departments: School of Life Sciences > Biology and Environmental Science
Subjects: Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics
Q Science > QL Zoology > QL0360 Invertebrates > QL0434 Arthropoda > QL0463 Insects
Depositing User: Library Cataloguing
Date Deposited: 20 Mar 2012 15:39
Last Modified: 25 Aug 2015 13:12
URI: http://sro.sussex.ac.uk/id/eprint/38117

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