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    A Kinome RNAi Screen in Drosophila Identifies Novel Genes Interacting with Lgl, aPKC, and Crb Cell Polarity Genes in Epithelial Tissues

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    Author
    Parsons, LM; Grzeschik, NA; Amaratunga, K; Burke, P; Quinn, LM; Richardson, HE
    Date
    2017-08-01
    Source Title
    G3: Genes, Genomes, Genetics
    Publisher
    GENETICS SOCIETY AMERICA
    University of Melbourne Author/s
    Richardson, Helena; Parsons, Linda; Quinn, Leonie
    Affiliation
    Anatomy and Neuroscience
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Parsons, L. M., Grzeschik, N. A., Amaratunga, K., Burke, P., Quinn, L. M. & Richardson, H. E. (2017). A Kinome RNAi Screen in Drosophila Identifies Novel Genes Interacting with Lgl, aPKC, and Crb Cell Polarity Genes in Epithelial Tissues. G3-GENES GENOMES GENETICS, 7 (8), pp.2497-2509. https://doi.org/10.1534/g3.117.043513.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/256202
    DOI
    10.1534/g3.117.043513
    Abstract
    In both Drosophila melanogaster and mammalian systems, epithelial structure and underlying cell polarity are essential for proper tissue morphogenesis and organ growth. Cell polarity interfaces with multiple cellular processes that are regulated by the phosphorylation status of large protein networks. To gain insight into the molecular mechanisms that coordinate cell polarity with tissue growth, we screened a boutique collection of RNAi stocks targeting the kinome for their capacity to modify Drosophila "cell polarity" eye and wing phenotypes. Initially, we identified kinase or phosphatase genes whose depletion modified adult eye phenotypes associated with the manipulation of cell polarity complexes (via overexpression of Crb or aPKC). We next conducted a secondary screen to test whether these cell polarity modifiers altered tissue overgrowth associated with depletion of Lgl in the wing. These screens identified Hippo, Jun kinase (JNK), and Notch signaling pathways, previously linked to cell polarity regulation of tissue growth. Furthermore, novel pathways not previously connected to cell polarity regulation of tissue growth were identified, including Wingless (Wg/Wnt), Ras, and lipid/Phospho-inositol-3-kinase (PI3K) signaling pathways. Additionally, we demonstrated that the "nutrient sensing" kinases Salt Inducible Kinase 2 and 3 (SIK2 and 3) are potent modifiers of cell polarity phenotypes and regulators of tissue growth. Overall, our screen has revealed novel cell polarity-interacting kinases and phosphatases that affect tissue growth, providing a platform for investigating molecular mechanisms coordinating cell polarity and tissue growth during development.

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