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Title: Proneural protein specificity in Drosophila melanogaster
Author: Maung, Saw Myat Thanda Win
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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Proneural genes are required for neural competence and subtype specification. I have investigated the nature of this subtype specificity by analysing the number, type and pattern of ectopic sense organ precursors produced by proneural gene misexpression in transformant flies. The bHLH domains of Atonal and Amos share 88% identity, however these proneural proteins have very different wildtype functions. Moreover, I show that they have abundantly distinct misexpression phenotypes. Importantly, I show that an apparent overlap in function is actually due to cross-activation of atonal by amos. I have investigated the functional specificity of amos with regard to atonal and scute by constructing chimeric proteins of Amos and Atonal, and also Amos and Scute. All previously published studies concerning sub-type specificity have concluded that the bHLH domain is the determining factor in all bHLH proteins. Contrary to published studies, I found that Atonal specificity is determined to a large extent by its non-bHLH sequence. Reciprocally, the non-bHLH region of Amos can also facilitate Amos functions. However these results are only valid in the context of an Atonal-like bHLH domain. Phenotypic analysis of Amos and Scute chimeras has reiterated the requirement for the Amos bHLH domain for Amos-like function and correspondingly the Scute bHLH domain for Scute-like function. In synopsis I conclude that subtype information is contained within the bHLH domains of highly divergent proneural proteins such as Amos and Scute; however closely related proneural proteins such as Amos and Atonal require elements outside the bHLH domain for complete subtype specification. I propose a model in which these sequence elements function via interaction with specificity co-factor proteins.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available