title: Novel regulators of planar cell polarity: a genetic analysis in Drosophila.
abstract: Planar cell polarity (PCP) is a common feature of many epithelia and epithelial organs. Although progress has been made in the dissection of molecular mechanisms regulating PCP, many questions remain. Here we describe a screen to identify novel PCP regulators in Drosophila. We employed mild gain-of-function (GOF) phenotypes of two cytoplasmic Frizzled (Fz)/PCP core components, Diego (Dgo) and Prickle (Pk), and screened these against the DrosDel genome-wide deficiency collection for dominant modifiers. Positive genomic regions were rescreened and narrowed down with smaller overlapping deficiencies from the Exelixis collection and RNAi-mediated knockdown applied to individual genes. This approach isolated new regulators of PCP, which were confirmed with loss-of-function analyses displaying PCP defects in the eye and/or wing. Furthermore, knockdown of a subset was also sensitive to dgo dosage or dominantly modified a dishevelled (dsh) GOF phenotype, supporting a role in Fz/PCP-mediated polarity establishment. Among the new "PCP" genes we identified several kinases, enzymes required for lipid modification, scaffolding proteins, and genes involved in substrate modification and/or degradation. Interestingly, one of them is a member of the Meckel-Gruber syndrome factors, associated with human ciliopathies, suggesting an important role for cell polarity in nonciliated cells.
authors.affiliation: Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Ursula
authors.initials: U
authors.lastname: Weber
authors.forename: William J
authors.initials: WJ
authors.lastname: Gault
authors.forename: Patricio
authors.initials: P
authors.lastname: Olguin
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Serysheva
authors.forename: Marek
authors.initials: M
authors.lastname: Mlodzik
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology*; D019295:Computational Biology; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics* / Q000378:metabolism; D005123:Eye / Q000033:anatomy & histology / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D015398:Signal Transduction; D014921:Wings, Animal / Q000033:anatomy & histology / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins