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Title: Small GTPase regulation in epithelial polarity remodelling and morphogenesis
Author: Massey, Katherine
ISNI:       0000 0004 7970 6558
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Small GTPases are a class of proteins implicated in the regulation of a wide range of processes in epithelial cells, from cell polarity and adhesion to migration. These proteins exist in `on' and `off' states, the transition between which is controlled by GEFs and GAPs. In particular, the RhoGTPases Rho1 and Cdc42 are required for many essential developmental programs in epithelial cells and tissues. Cdc42 is a key regulator of apical-basal polarity in epithelial cells. In its active form it supports Par6-aPKC recruitment at the apical pole of epithelial cells, which allows for separation of apical and junctional domains. This process is required for apical differentiation and cell-cell adhesion. Rho1 is also required for the integrity of adhesion junctions in Drosophila epithelial cells. As well as their role in cell polarity, both Cdc42 and Rho1 have been shown to antagonise each other to regulate the apical area and geometry of epithelial cells. The Drosophila retina is an ideal model system in which to study RhoGTPase function in epithelial polarity and morphogenesis, and how they relate to cell adhesions and the cytoskeleton. However, the GEFs and GAPs regulating Cdc42 and Rho1 during epithelial polarity and apical area determination are unknown. During my Thesis I have addressed this issue by performing a reverse genetic screen in the fly retina. I identified and characterised three potential regulators of RhoGTPases and sought to connect them to Cdc42 and Rho1, as well as fit them into the wider context of retinal development and morphogenesis. In addition I have generated and characterized de novo mutations for each of these genes using CRISPR/Cas9 technology.
Supervisor: Pichaud, F. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available