TY - JOUR T1 - Functional genomic analysis of the Wnt-wingless signaling pathway. JF - Science Y1 - 2005 A1 - DasGupta, Ramanuj A1 - Kaykas, Ajamete A1 - Moon, Randall T A1 - Perrimon, Norbert KW - Animals KW - beta Catenin KW - Binding Sites KW - Cell Line KW - Cloning, Molecular KW - Computational Biology KW - Cytoskeletal Proteins KW - drosophila melanogaster KW - Drosophila Proteins KW - Embryo, Nonmammalian KW - Embryonic Development KW - Epistasis, Genetic KW - Gene Expression Regulation KW - Genes, Insect KW - Genes, Reporter KW - Genomics KW - Mutation KW - Phenotype KW - Phosphorylation KW - Protein Kinases KW - Proteins KW - Proto-Oncogene Proteins KW - rab5 GTP-Binding Proteins KW - RNA Interference KW - Signal Transduction KW - Trans-Activators KW - Transcription Factors KW - Transfection KW - Wnt Proteins KW - Wnt1 Protein KW - Wnt3 Protein KW - zebrafish KW - Zebrafish Proteins AB -

The Wnt-Wingless (Wg) pathway is one of a core set of evolutionarily conserved signaling pathways that regulates many aspects of metazoan development. Aberrant Wnt signaling has been linked to human disease. In the present study, we used a genomewide RNA interference (RNAi) screen in Drosophila cells to screen for regulators of the Wnt pathway. We identified 238 potential regulators, which include known pathway components, genes with functions not previously linked to this pathway, and genes with no previously assigned functions. Reciprocal-Best-Blast analyses reveal that 50% of the genes identified in the screen have human orthologs, of which approximately 18% are associated with human disease. Functional assays of selected genes from the cell-based screen in Drosophila, mammalian cells, and zebrafish embryos demonstrated that these genes have evolutionarily conserved functions in Wnt signaling. High-throughput RNAi screens in cultured cells, followed by functional analyses in model organisms, prove to be a rapid means of identifying regulators of signaling pathways implicated in development and disease.

VL - 308 IS - 5723 U1 - http://www.ncbi.nlm.nih.gov/pubmed/15817814?dopt=Abstract ER -