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Genome-wide analysis of Notch signalling in Drosophila by transgenic RNAi
Open accessAbstract
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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“A powerful approach to investigating gene function in Drosophila is to knockdown its expression with RNAi and assess the biological consequences [29,30].”
From Functional unknomics: Systematic screening of conserved genes of unknown function (2023) · cites this paper as [30]
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Metadata
- Authors
- Mummery-Widmer, J. L., Yamazaki, M., Stoeger, T., Novatchkova, M., Bhalerao, S., Chen, D., Dietzl, G., Dickson, B. J., & Knoblich, J. A.
- Affiliations
- Institute of Molecular Biotechnology (AT)
- Max Perutz Labs (AT)
- Research Institute of Molecular Pathology (AT)
- Corresponding author
- Knoblich, Juergen A.
- ORCID
- Venue
- Nature
- Published
- 2009-04
- Volume
- 458
- Issue
- 7241
- Pages
- 987-992
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2988197
- OpenAlex
- W2118810801
- Cited by
- 305
- References
- 54
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 5 · 2023: 10 · 2022: 13 · 2021: 15 · 2020: 14 · 2019: 11 · 2018: 16 · 2017: 16 · 2016: 24 · 2015: 24 · 2014: 29 · 2013: 30 · 2012: 24
- FWCI
- 10.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- Notch signaling, Drosophila, genome-wide RNAi screen, asymmetric cell division, protein-protein interaction network, COP9 signalosome, loss-of-function phenotypes
- MeSH terms
- Animals, Cell Division, Drosophila melanogaster, Phenotype, Quality Control, Signal Transduction, Active Transport, Cell Nucleus, Drosophila Proteins, Animals, Genetically Modified, RNA Interference, Genome, Insect, Receptors, Notch
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