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

Author

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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,
    Present address: The Global COE program, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.)

  • 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,
    Research Institute of Molecular Pathology (IMP), Dr Bohr-Gasse 7, and,)

  • Sheetal Bhalerao

    (Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr-Gasse 3,
    Research Institute of Molecular Pathology (IMP), Dr Bohr-Gasse 7, and,)

  • 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,)

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.

Suggested Citation

  • Jennifer L. Mummery-Widmer & Masakazu Yamazaki & Thomas Stoeger & Maria Novatchkova & Sheetal Bhalerao & Doris Chen & Georg Dietzl & Barry J. Dickson & Juergen A. Knoblich, 2009. "Genome-wide analysis of Notch signalling in Drosophila by transgenic RNAi," Nature, Nature, vol. 458(7241), pages 987-992, April.
    • Handle: RePEc:nat:nature:v:458:y:2009:i:7241:d:10.1038_nature07936
    DOI: 10.1038/nature07936
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    Cited by:

    1. Asmundur Oddsson & Patrick Sulem & Gardar Sveinbjornsson & Gudny A. Arnadottir & Valgerdur Steinthorsdottir & Gisli H. Halldorsson & Bjarni A. Atlason & Gudjon R. Oskarsson & Hannes Helgason & Henriet, 2023. "Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Robert Stojnic & Audrey Qiuyan Fu & Boris Adryan, 2012. "A Graphical Modelling Approach to the Dissection of Highly Correlated Transcription Factor Binding Site Profiles," PLOS Computational Biology, Public Library of Science, vol. 8(11), pages 1-13, November.
    3. Oksana Netschitailo & Yidong Wang & Anna Wagner & Vivien Sommer & Eveline C. Verhulst & Martin Beye, 2023. "The function and evolution of a genetic switch controlling sexually dimorphic eye differentiation in honeybees," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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