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Title: Rap1 is a main regulator of Adherens junction remodelling in the fly retina
Author: Burki, M.
ISNI:       0000 0004 7231 5095
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2017
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During epithelial cell polarisation, the conserved apical and lateral polarity proteins set up the position of the Zonula Adherens (ZA), which consists of a circumferential belt of Adherens Junction (AJ) material, and thus define the apical and lateral domains of the cell. During my thesis, I have tried to uncover the genes that are involved in the transcriptional control of polarity remodelling and ZA morphogenesis during development. To this end, I used the genetically amenable Drosophila retina to carry out transcriptional profiling at the onset of photoreceptor polarity remodelling. With this approach, I was able to uncover several genes that seem to be regulated during polarity remodelling, including the zinc finger transcription factor ovo, which might regulate photoreceptor morphogenesis through regulation of the actin cytoskeleton. In addition to the transcriptional control of epithelial polarity, I made use of the fly photoreceptor to uncover new cellular and molecular pathways that promote AJ morphogenesis during ZA assembly. Using a candidate-based approach, I identified the small GTPase protein Rap1 as an important regulator of AJ morphogenesis, through stabilisation of DE-Cad at the developing ZA. In this context, I found that rap1 functions with the p21-activated kinase pak4 to promote AJ material accumulation at the developing ZA. Finally, in order to discover new genes and mechanisms that might link rap1 to the epithelial gene network, I made use of rap1 RNAi, to conduct a large-scale genetic modifier screen. This genetic screen led to the identification of several ubiquitin-related genes that genetically interact with rap1 and therefore might be involved in rap1-dependent polarity remodelling and ZA morphogenesis.
Supervisor: Pichaud, F. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available