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Molecular diversity of Dscam: recognition of molecular identity in neuronal wiring

Abstract

Our understanding of how the enormously complex task of interconnecting millions of nerve cells is accomplished remains rudimentary. What molecular mechanisms control its exquisite specificity? Can we pinpoint single molecular interactions that might help to explain some of the specificity requirements that underlie neuronal wiring? A series of recent studies on the molecular diversity of the Drosophila melanogaster cell-surface receptor Down syndrome cell-adhesion molecule (Dscam) provide one exceptional example of a novel mechanistic model of neuronal-wiring specificity, progressing from structural studies of single protein–protein interactions to biochemical analysis in vitro and to an understanding of complex neuronal differentiation at the single-cell or tissue levels.

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Figure 1: Dscam gene structure and protein architecture.
Figure 2: Principles of isoform-specific homophilic binding of Dscam.
Figure 3: Homophilic recognition of identical Dscam isoforms mediates repulsion and dendrite self-avoidance.

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Schmucker, D. Molecular diversity of Dscam: recognition of molecular identity in neuronal wiring. Nat Rev Neurosci 8, 915–920 (2007). https://doi.org/10.1038/nrn2256

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