1. Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr-Gasse 3,
2. Research Institute of Molecular Pathology (IMP), Dr Bohr-Gasse 7, and,
3. Max F. Perutz Laboratories (MFPL), Department of Biochemistry, Dr Bohr-Gasse 9, A-1030 Vienna, Austria
4. These authors contributed equally to this work.
5. Present address: The Global COE program, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.

Correspondence to: Juergen A. Knoblich¹ Correspondence and requests for materials should be addressed to J.A.K. (Email: juergen.knoblich@imba.oeaw.ac.at).

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.

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