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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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posted on 31.03.2022, 02:57 by Linda M Parsons, Nicola A Grzeschik, Kasun Amaratunga, Peter BurkePeter Burke, Leonie M Quinn, Helena RichardsonHelena Richardson
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.

Funding

This work was funded by a Contributing to Australian Scholarship and Science Foundation Science and Medicine Grant (SM-14-5398) awarded to L.M.P. and National Health and Medical Research Council (NHMRC) Project grant 628401 awarded to H.E.R. and N.G. H.E.R. was supported by a NHMRC fellowship (1020056), and funds from La Trobe University and the La Trobe Institute of Molecular Science.

History

Publication Date

01/01/2017

Journal

G3: Genes, Genomes, Genetics

Volume

7

Issue

8

Pagination

13p. (p. 2497-2509)

Publisher

Oxford University Press

ISSN

2160-1836

Rights Statement

© 2017 Parsons et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/ licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.