title: Systematic screening of a Drosophila ORF library in vivo uncovers Wnt/Wg pathway components.
abstract: We created a site-directed UAS-ORF library of 655 growth-regulating genes in Drosophila. This library represents a large collection of genes regulating cell cycle, cell size, and proliferation and will be a valuable resource for studying growth regulation in vivo. By using misexpression of genes, we prevent problems arising from genetic redundancy and can uncover novel gene functions. To validate the usefulness of this library, we screened for Wingless (Wg) pathway components. We used a combination of experimental and bioinformatic approaches to predict candidates and identified three serine/threonine kinases as regulators of Wg signaling. We show that one of these, Nek2, optimizes pathway response by direct phosphorylation of Dishevelled. In addition, we describe functional relations for roughly 5% of all Drosophila genes and identify a large number of genes that regulate cell size, proliferation, and final organ size upon misexpression.
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich 8057, Switzerland.
authors.forename: Claus
authors.initials: C
authors.lastname: Schertel
authors.forename: Dashun
authors.initials: D
authors.lastname: Huang
authors.forename: Mikael
authors.initials: M
authors.lastname: Björklund
authors.forename: Johannes
authors.initials: J
authors.lastname: Bischof
authors.forename: Dingzi
authors.initials: D
authors.lastname: Yin
authors.forename: Rongxia
authors.initials: R
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Wu
authors.forename: Rong
authors.initials: R
authors.lastname: Zeng
authors.forename: Jiarui
authors.initials: J
authors.lastname: Wu
authors.forename: Jussi
authors.initials: J
authors.lastname: Taipale
authors.forename: Haiyun
authors.initials: H
authors.lastname: Song
authors.forename: Konrad
authors.initials: K
authors.lastname: Basler
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019295:Computational Biology; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D016366:Open Reading Frames / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D051155:Wnt1 Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D010750:Phosphoproteins; D051153:Wnt Proteins; D051155:Wnt1 Protein; C000606588:dsh protein, Drosophila; C074622:wg protein, Drosophila; D008156:Luciferases