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Cell-intrinsic requirement of Dscam1 isoform diversity for axon collateral formation

Science  06 Jun 2014:
Vol. 344, Issue 6188, pp. 1182-1186
DOI: 10.1126/science.1251852

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Wiring the developing insect brain

Developmental brain wiring requires a complex set of cellular interactions often orchestrated by a large number of surface receptors. Thousands of Dscam1 receptor isoforms function as “surface tags” endowing neurons with unique molecular identities. These isoforms are important for neuronal self-recognition and dendrite self-avoidance. He et al. report that the diversity of Dscam1 isoforms is also essential for complex axonal branching of sensory neurons in developing fruit flies.

Science, this issue p. 1182

Abstract

The isoform diversity of the Drosophila Dscam1 receptor is important for neuronal self-recognition and self-avoidance. A canonical model suggests that homophilic binding of identical Dscam1 receptor isoforms on sister dendrites ensures self-avoidance even when only a single isoform is expressed. We detected a cell-intrinsic function of Dscam1 that requires the coexpression of multiple isoforms. Manipulation of the Dscam1 isoform pool in single neurons caused severe disruption of collateral formation of mechanosensory axons. Changes in isoform abundance led to dominant dosage-sensitive inhibition of branching. We propose that the ratio of matching to nonmatching isoforms within a cell influences the Dscam1-mediated signaling strength, which in turn controls axon growth and growth cone sprouting. Cell-intrinsic use of surface receptor diversity may be of general importance in regulating axonal branching during brain wiring.

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