Cited by 235Axon Guidance and Neuronal SignalingDevelopmental Biology and Gene RegulationNeurobiology and Insect Physiology Research

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Dscam diversity is essential for neuronal wiring and self-recognition

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Hattori, Daisuke, Demir, Ebru, Kim, Ho Won, Viragh, Erika, Zipursky, S. Lawrence, Dickson, Barry J.·2007·Nature

DOI 10.1038/nature06099PMC PMC2691715

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Abstract

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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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.
ORCID: Hattori, Daisuke
Demir, Ebru
Zipursky, S. Lawrence
Dickson, Barry J.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2007-09-13
Volume: 449
Issue: 7159
Pages: 223-227
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature06099
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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

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Dscam diversity is essential for neuronal wiring and self-recognition

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