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Title: Dynamics of the core planar polarity proteins and their role in morphogenesis in Drosophila
Author: Warrington, Samantha Jane
ISNI:       0000 0004 5348 8759
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2014
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Signalling through the Frizzled-dependent planar polarity pathway is a conserved mechanism that polarises cells in a plane perpendicular to the apical-basal axis. Epithelial cells in many organisms exhibit planar polarity, including the Drosophila wing and eye, and during convergent extension movements in vertebrates. The core planar polarity proteins involved in establishing planar polarity exhibit asymmetric subcellular localisations. Currently little is known about how the asymmetry is generated and maintained. This work uses techniques such as live imaging and FRAP of Drosophila epithelial tissues to study protein turnover, to understand these processes. I focused on the core proteins Frizzled (Fz) and Flamingo (Fmi). Both proteins are localised at apical junctions in membrane subdomains (puncta). FRAP on puncta of either protein shows there is a large immobile fraction compared to surrounding junctional regions. Mutations in the other core proteins result in a loss of Fz and Fmi protein asymmetry, a loss of large puncta, as well as a reduction in the size of the immobile fraction. My data support a model where the six known core proteins are mutually stabilised by each other into large puncta where they form intercellular asymmetric junctional complexes. These puncta represent groups of aligned intercellular protein complexes, which I propose are required for establishing and coupling cellular asymmetry. The roles of planar polarity during coordinated cell rearrangements have not been extensively studied in Drosophila. This work shows that the core proteins are required for coordinated cell rearrangements during Drosophila embryonic tracheal cell intercalation. Regulation of the adhesion protein DE-cadherin is required for cell intercalation and this is under control of the core proteins via a RhoGEF2-dependent mechanism. Therefore this work supports a role for the core proteins in regulating cell adhesion during cell movements.
Supervisor: Strutt, David Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available