Ectopic expression of mnb and Hip1 alters Drosophila development

MacDonald, Jillian M. (Jillian Michelle). (2008) Ectopic expression of mnb and Hip1 alters Drosophila development. Masters thesis, Memorial University of Newfoundland.

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Abstract

A powerful approach to studying the mechanisms of disease is through the use of transgenic models like Drosophila melanogaster. The Drosophila homologue of the human Down syndrome candidate gene, Dyrk1A, is minibrain (mnb). Studies have shown that mnb can participate in development of the Drosophila eye to control growth and survival through modification of insulin receptor signalling. Huntingtin-interacting protein 1 (Hip1), which differentially interacts with the mutant and normal forms of the Huntington disease protein, huntingtin, has been shown to play a role in Drosophila neurogenesis. There are two naturally occurring versions of the Hip1 protein, a full length version and a truncated version missing the N-terminal ANTH domain, referred to as Hip1ΔANTH. As a biochemical interaction has been identified between Hip1 and Dyrk1A/mnb, this study examines these two genes in Drosophila development. In this study the UAS-Ga14 system was utilized to direct the expression of Dyrk1A/mnb, Hip1 and components of the insulin signalling pathway, akt & foxo1, in the developing dorsal notum and eye. While neither mnb nor foxo1 over-expression has any effect, we found that over-expression of akt, a component of the insulin signalling pathway, increases the microchaetae density on the dorsal notum. The over-expression of mnb and Hip1 in the eye have no effect on eye development. Under the sensitized growth conditions where the GMRGa14 also drives the UASfoxo11 transgene, the full length versions of Hip1 show decreased bristle number and decreased ommatidia number while the truncated versions of Hip1 lacking the lipid-binding ANTH domain show decreased ommatidia number. Over-expression of mnb and Hip1 together with foxo1 show changes in eye development, indicating a possible interaction between these two genes. As these are genes in two completely different diseases, finding how they interact could provide a key insight into finding therapies for neurodegenerative diseases.

Item Type: Thesis (Masters)
URI: http://research.library.mun.ca/id/eprint/8771
Item ID: 8771
Additional Information: Includes bibliographical references (leaves 96-105)
Department(s): Science, Faculty of > Biology
Date: 2008
Date Type: Submission
Library of Congress Subject Heading: Developmental neurobiology; Drosophila melanogaster--Growth; Protein kinases; Protein-protein interactions; Proteins--Physiological effect

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