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PMID:23583758

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Citation

Schertel, C, Huang, D, Björklund, M, Bischof, J, Yin, D, Li, R, Wu, Y, Zeng, R, Wu, J, Taipale, J, Song, H and Basler, K (2013) Systematic screening of a Drosophila ORF library in vivo uncovers Wnt/Wg pathway components. Dev. Cell 25:207-19

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.

Links

PubMed Online version:10.1016/j.devcel.2013.02.019

Keywords

Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Animals; Computational Biology; Dishevelled Proteins; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster/genetics; Drosophila melanogaster/growth & development; Drosophila melanogaster/metabolism; Embryo, Nonmammalian/cytology; Embryo, Nonmammalian/metabolism; Gene Expression Regulation, Developmental; Gene Library; Immunoenzyme Techniques; Luciferases/metabolism; Open Reading Frames/genetics; Phosphoproteins/genetics; Phosphoproteins/metabolism; Phosphorylation; Signal Transduction; Wnt Proteins/genetics; Wnt Proteins/metabolism; Wnt1 Protein/genetics; Wnt1 Protein/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:O62602

involved_in

GO:0090090: negative regulation of canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:DCO

involved_in

GO:0030177: positive regulation of Wnt signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0029970

P

Seeded From UniProt

complete

DROME:Q9W3N8

enables

GO:0004674: protein serine/threonine kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:Q9W3N8

involved_in

GO:0006468: protein phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9W3N8

involved_in

GO:0090263: positive regulation of canonical Wnt signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0284084

P

Seeded From UniProt

complete

DROME:Q9W3N8

involved_in

GO:0090263: positive regulation of canonical Wnt signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0000499

P

Seeded From UniProt

complete

DROME:DYRK2

involved_in

GO:0030177: positive regulation of Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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