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Dscam diversity is essential for neuronal wiring and self-recognition
Open accessAbstract
Neurons are thought to use diverse families of cell-surface molecules for cell recognition during circuit assembly. In Drosophila, alternative splicing of the Down syndrome cell adhesion molecule (Dscam) gene potentially generates 38,016 closely related transmembrane proteins of the immunoglobulin superfamily, each comprising one of 19,008 alternative ectodomains linked to one of two alternative transmembrane segments. These ectodomains show isoform-specific homophilic binding, leading to speculation that Dscam proteins mediate cell recognition. Genetic studies have established that Dscam is required for neural circuit assembly, but the extent to which isoform diversity contributes to this process is not known. Here we provide conclusive evidence that Dscam diversity is essential for circuit assembly. Using homologous recombination, we reduced the entire repertoire of Dscam ectodomains to just a single isoform. Neural circuits in these mutants are severely disorganized. Furthermore, we show that it is crucial for neighbouring neurons to express distinct isoforms, but that the specific identity of the isoforms expressed in an individual neuron is unimportant. We conclude that Dscam diversity provides each neuron with a unique identity by which it can distinguish its own processes from those of other neurons, and that this self-recognition is essential for wiring the Drosophila brain.
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“It is known that, even within the same system, such as the fly olfactory pathway, some neuronal wiring is highly specific and molecularly programmed (Hattori et al., 2007; Hong and Luo, 2014), while other wiring is effectively random (Caron et al., 2013), and yet other wiring is learned (Aso et al., 2014a).”
From Toward an integration of deep learning and neuroscience (2016) · cites this paper as Hattori et al., 2007
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Metadata
- Authors
- Hattori, D., Demir, E., Kim, H. W., Viragh, E., Zipursky, S. L., & Dickson, B. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Research Institute of Molecular Pathology (AT)
- Corresponding author
- Zipursky, S. Lawrence
- Dickson, Barry J.
- Venue
- Nature
- Published
- 2007-09-13
- Volume
- 449
- Issue
- 7159
- Pages
- 223-227
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2691715
- OpenAlex
- W2000103717
- Cited by
- 225
- References
- 28
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 4 · 2023: 15 · 2022: 12 · 2021: 6 · 2020: 8 · 2019: 12 · 2018: 11 · 2017: 7 · 2016: 12 · 2015: 18 · 2014: 11 · 2013: 13 · 2012: 7
- FWCI
- 7.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- 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
- Keywords
- Dscam, Down syndrome cell adhesion molecule, alternative splicing, immunoglobulin superfamily, homophilic binding, mosaic analysis, Drosophila central nervous system, isoform diversity
- MeSH terms
- Alleles, Animals, Brain, Drosophila melanogaster, Mutation, Neurons, Cell Adhesion Molecules, Alternative Splicing, Protein Isoforms, Mushroom Bodies, Drosophila Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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