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Title: The regulation of the Drosophila enhancer of split genes, md and mg
Author: Cooper, M. T. D.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1999
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In Drosophila, the targets of Notch signalling include seven genes in the Enhancer of split complex [E(spl)-C] which are required to bring about some of the effects of Notch signalling. Expression of these genes is induced in response to Notch, but only in a subset of the places that the Notch signalling pathway is known to be active. The differential regulation of the E(spl) genes and of the other target genes may explain why Notch signalling is able to act as an inductive signal and prohibitive signal in different cellular contexts. The main aim of the research was to understand the control of expression of two members of the E(spl)-C, mδ and mγ. The results demonstrate that these genes are controlled at the level of transcription, with local upstream enhancers being above to drive the expression of a reporter gene in patterns similar to the endogeneous genes. However, the enhancers do not completely recapitulate the endogenous gene expression. In addition some elements appear to be acting on both and to confer the correct expression of both genes. This provides an explanation for why the E(spl)-C is conserved between different species of Drosophila. Both the Notch signalling pathway and proneural proteins are involved in regulating and . However, neither are sufficient and it appears that there are additional repressor and activator proteins needed to specify the correct expression of these genes. The expression of one of the reporter genes also suggests that the E(spl) genes might need a mechanism for inactivation independent of Notch. Expression of the same reporter gene revealed that Notch signalling acts downstream of Frizzled signalling during the R3/4 cell fate decision in the developing eye. Further analysis of the event has illustrated the importance of intracellular modulators of Notch signalling in regulating the expression of target genes, and the role of Notch in binary cell fate decisions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available