Robust discrimination between self and non-self neurites requires thousands of Dscam1 isoforms

Daisuke Hattori, Yi Chen, Benjamin J. Matthews, Lukasz Salwinski, Chiara Sabatti, Wesley B. Grueber and S. Lawrence Zipursky ()
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Daisuke Hattori: Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA
Yi Chen: Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA
Benjamin J. Matthews: Center for Neurobiology and Behavior, Columbia University Medical Center, New York, New York 10032, USA
Lukasz Salwinski: UCLA-DOE Institute for Genomics and Proteomics, Howard Hughes Medical Institute, Molecular Biology Institute, Los Angeles, California 90095, USA
Chiara Sabatti: David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA
Wesley B. Grueber: Columbia University Medical Center, New York, New York 10032, USA
S. Lawrence Zipursky: Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA

Nature, 2009, vol. 461, issue 7264, 644-648

Abstract: Discriminating neurites need multiple Dscam1 isoforms In fruitfly nerve cells, alternative splicing of the Dscam gene's messenger RNA produces a remarkable variety of cell-surface proteins — presenting some 19,000 different extracellular domains. Each isoform is capable of binding exclusively to itself, thus promoting repulsion among neuronal processes extended by the same neuron. This process of neurite self-avoidance is important in helping to direct dendritic and axonal branching appropriately. By generating mutant flies with graded reductions in the number of Dscam isoforms, Larry Zipursky and his team have now determined that at least 1,000 but no more than 5,000 isoforms are essential to provide a robust mechanism of neuronal self-avoidance during brain wiring. How this translates into vertebrate brain development remains unclear, as vertebrate Dscam genes produce just a handful of distinct isoforms.

Date: 2009
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DOI: 10.1038/nature08431

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