Epithelial polarity and cell signalling during the development of the Drosophila melanogaster eye.
Doctoral thesis, UCL (University College London).
Crumbs is a conserved polarity protein involved in establishing apical polarity in epithelial cells. In this study the link between Crumbs and cell signalling has been examined. Patj, which is a component or the complex of proteins that interact with Crumbs, has also been investigated with respect to cell signalling. In addition, a screen has been developed to identify novel regulators of cell polarity. I have used the developing eye of Drosophila melanogaster to undertake this work, as it provides a genetically amenable model system for studying polarised epithelial cells. In the first section, I show that Crumbs itself is required for proper organ size control during Drosophila head development. Loss of crumbs function results in an increase in cell proliferation in the eye imaginal disc, which leads to the development of flies with larger eyes and heads. This overgrowth phenotype is dependent on Notch signalling and my data show that Crumbs acts as a negative regulator of Notch signalling during eye imaginal disc development. My findings suggest a role for Crumbs in modulating endocytosis, which is key to regulating ligand-dependent transactivation of the Notch receptor. This work reveals a novel function for crumbs in organ size control during Drosophila head development and in regulating Notch signaling through endocytosis. The second section focuses on Patj, and its potential role in regulating growth during pupal eye development. The evidence I have suggests that this may be through modulation of the Target of Rapamycin (TOR) growth signalling pathway via Tuberous Scelrosis Complex 2. Finally, I present work about an in vivo screening process in the adult Drosophila eye. This uses RNA interference and a phenomenon called the deep pseudo pupil to screen for genes involved in polarity and cytoskeletal architecture of photoreceptor cells. The pilot screen undertaken here demonstrates that this is a viable and effective approach for detecting polarity defects in the photoreceptor.
|Title:||Epithelial polarity and cell signalling during the development of the Drosophila melanogaster eye|
|Additional information:||Authorisation for digitisation not received|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Cell and Developmental Biology|
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