Pradhan, Tirthadipa (2011) Function and regulation of the Drosophila planar polarity effector Multiple Wing Hairs (Mwh). MPhil thesis, University of Sheffield.
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The noncanonical Frizzled signalling pathway regulates planar cell polarity (PCP) in both vertebrates and invertebrates. In the Drosophila wing, asymmetric subcellular localisation of PCP proteins specifies the production of a single distally pointing trichome in each cell. The localisation of core PCP proteins (Fz, Dsh, Dgo, Stbm, Pk and Fmi) at the proximal and distal cell edge acts as a cue for establishment of a polarisation event mediated by the effector proteins Inturned (In), Fuzzy (Fy), Fritz (Frtz), and Multiple wing hairs (Mwh). Mwh, the most downstream effector protein known of the PCP pathway, localises at the apicoproximal membrane domain of each wing cell just before trichome formation. In its absence, ectopic actin bundle formation occurs over the entire apical surface of the cell, resulting in the formation of multiple trichomes with abnormal polarity. There is limited understanding of how Mwh accumulates proximally in each wing cell and about its interaction with the cytoskeleton. To fill the gap in our knowledge I did an in vivo RNAi screen in the Drosophila wing, in order to search for novel regulators of Mwh. My screening has found several potential genes (such as c12.1, Mo25, Rab23, staufen, sep2, cip4, Tsp29Fb, formin3) that alter the distribution of Mwh protein and may therefore regulate it directly. Additionally, other genes were found which appears to have a potential role in regulating cell size, timing of trichome formation and trichome morphology. Bioinformatic analysis has revealed the presence of a GBD/FH3 domain in Mwh, which is normally found in the Formin group of cytoskeletal regulatory proteins. In an in vitro study in mammalian fibroblast cells (3T3), the GBD domain of Mwh was found to induce cytoskeletal changes such as a significant reduction of stress fibres, suggesting a possible role for the GBD domain of Mwh in modulating the cell cytoskeleton. Further investigation will provide better understanding of the pathway that leads to the formation of a single distally pointing trichome downstream of the core PCP cues, and also how Mwh regulates this pathway by modifying the actin cytoskeleton.
|Item Type:||Thesis (MPhil)|
|Academic Units:||The University of Sheffield > Faculty of Science (Sheffield) > Biomedical Science (Sheffield)
The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Biomedical Science (Sheffield)
|Depositing User:||Miss Tirthadipa Pradhan|
|Date Deposited:||19 Dec 2011 16:27|
|Last Modified:||08 Aug 2013 08:47|