Systematic screening of a Drosophila ORF library in vivo uncovers Wnt/Wg pathway components

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.