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Genome-wide analysis of Notch signalling in Drosophila by transgenic RNAi

2009; Nature Portfolio; Volume: 458; Issue: 7241 Linguagem: Inglês

10.1038/nature07936

1476-4687

Jennifer L. Mummery-Widmer, Masakazu Yamazaki, Thomas Stoeger, Maria Novatchkova, Sheetal Bhalerao, Doris Chen, Georg Dietzl, Barry J. Dickson, Juergen A. Knoblich,

Genomics and Phylogenetic Studies

Genome-wide RNA interference (RNAi) screens have identified near-complete sets of genes involved in cellular processes. However, this methodology has not yet been used to study complex developmental processes in a tissue-specific manner. Here we report the use of a library of Drosophila strains expressing inducible hairpin RNAi constructs to study the Notch signalling pathway during external sensory organ development. We assigned putative loss-of-function phenotypes to 21.2% of the protein-coding Drosophila genes. Using secondary assays, we identified 6 new genes involved in asymmetric cell division and 23 novel genes regulating the Notch signalling pathway. By integrating our phenotypic results with protein interaction data, we constructed a genome-wide, functionally validated interaction network governing Notch signalling and asymmetric cell division. We used clustering algorithms to identify nuclear import pathways and the COP9 signallosome as Notch regulators. Our results show that complex developmental processes can be analysed on a genome-wide level and provide a unique resource for functional annotation of the Drosophila genome. The Notch pathway, a ubiquitous cell signalling system found in most multicellular organisms, is an important regulator in the embryo and remains active in many tissues in the adult. Now a genome-wide analysis using a library of transgenic Drosophila strains that express RNA interference (RNAi) constructs for almost every gene in the fly genome has been used to study one of the best understood morphogenetic events in fruitfly development: the formation of external sensory organs. Using RNAi screening, genes thought to be involved in Notch interactions can be inactivated in a tissue specific manner. The resulting data make it possible to assign putative functions to about 20% of the protein-coding Drosophila genes and to identify six new genes involved in asymmetric cell division and twenty-three novel genes regulating the Notch signalling pathway. Knoblich and colleagues use a library of Drosophila strains expressing inducible hairpin RNA interference constructs to study the Notch signalling pathway during external sensory organ development. They assign putative loss-of-function phenotypes to 21.2% of the protein-coding Drosophila genes, identify 6 new genes involved in asymmetric cell division and 23 novel genes regulating the Notch signalling pathway.