Dscam diversity is essential for neuronal wiring and self-recognition

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

Research output: Contribution to journalArticle

138 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)223-227
Number of pages5
JournalNature
Volume449
Issue number7159
DOIs
StatePublished - Sep 13 2007
Externally publishedYes

Fingerprint

Cell Adhesion Molecules
Down Syndrome
Protein Isoforms
Neurons
Drosophila
Homologous Recombination
Alternative Splicing
Immunoglobulins
Proteins
Brain
Genes

ASJC Scopus subject areas

  • General

Cite this

Hattori, D., Demir, E., Kim, H. W., Viragh, E., Zipursky, S. L., & Dickson, B. J. (2007). Dscam diversity is essential for neuronal wiring and self-recognition. Nature, 449(7159), 223-227. https://doi.org/10.1038/nature06099

Dscam diversity is essential for neuronal wiring and self-recognition. / Hattori, Daisuke; Demir, Ebru; Kim, Ho Won; Viragh, Erika; Zipursky, S. Lawrence; Dickson, Barry J.

In: Nature, Vol. 449, No. 7159, 13.09.2007, p. 223-227.

Research output: Contribution to journalArticle

Hattori, D, Demir, E, Kim, HW, Viragh, E, Zipursky, SL & Dickson, BJ 2007, 'Dscam diversity is essential for neuronal wiring and self-recognition', Nature, vol. 449, no. 7159, pp. 223-227. https://doi.org/10.1038/nature06099
Hattori D, Demir E, Kim HW, Viragh E, Zipursky SL, Dickson BJ. Dscam diversity is essential for neuronal wiring and self-recognition. Nature. 2007 Sep 13;449(7159):223-227. https://doi.org/10.1038/nature06099
Hattori, Daisuke ; Demir, Ebru ; Kim, Ho Won ; Viragh, Erika ; Zipursky, S. Lawrence ; Dickson, Barry J. / Dscam diversity is essential for neuronal wiring and self-recognition. In: Nature. 2007 ; Vol. 449, No. 7159. pp. 223-227.
@article{cf0792c7fa8a45368f0da50e1d925f6d,
title = "Dscam diversity is essential for neuronal wiring and self-recognition",
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.",
author = "Daisuke Hattori and Ebru Demir and Kim, {Ho Won} and Erika Viragh and Zipursky, {S. Lawrence} and Dickson, {Barry J.}",
year = "2007",
month = "9",
day = "13",
doi = "10.1038/nature06099",
language = "English (US)",
volume = "449",
pages = "223--227",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7159",

}

TY - JOUR

T1 - Dscam diversity is essential for neuronal wiring and self-recognition

AU - Hattori, Daisuke

AU - Demir, Ebru

AU - Kim, Ho Won

AU - Viragh, Erika

AU - Zipursky, S. Lawrence

AU - Dickson, Barry J.

PY - 2007/9/13

Y1 - 2007/9/13

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34548612755&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548612755&partnerID=8YFLogxK

U2 - 10.1038/nature06099

DO - 10.1038/nature06099

M3 - Article

C2 - 17851526

AN - SCOPUS:34548612755

VL - 449

SP - 223

EP - 227

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7159

ER -