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

Jennifer L. Mummery-Widmer, Masakazu Yamazaki, Thomas Stoeger, Maria Novatchkova, Sheetal Bhalerao, Doris Chen, Georg Dietzl, Barry J. Dickson and Juergen A. Knoblich ()
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Jennifer L. Mummery-Widmer: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr-Gasse 3,
Masakazu Yamazaki: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr-Gasse 3,
Thomas Stoeger: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr-Gasse 3,
Maria Novatchkova: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr-Gasse 3,
Sheetal Bhalerao: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr-Gasse 3,
Doris Chen: Max F. Perutz Laboratories (MFPL), Dr Bohr-Gasse 9, A-1030 Vienna, Austria
Georg Dietzl: Research Institute of Molecular Pathology (IMP), Dr Bohr-Gasse 7, and,
Barry J. Dickson: Research Institute of Molecular Pathology (IMP), Dr Bohr-Gasse 7, and,
Juergen A. Knoblich: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr-Gasse 3,

Nature, 2009, vol. 458, issue 7241, 987-992

Abstract: Abstract 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.

Date: 2009
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DOI: 10.1038/nature07936

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