Neuron
Volume 70, Issue 5, 9 June 2011, Pages 951-965
Journal home page for Neuron

Article
VEGF Signaling through Neuropilin 1 Guides Commissural Axon Crossing at the Optic Chiasm

https://doi.org/10.1016/j.neuron.2011.02.052Get rights and content
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Summary

During development, the axons of retinal ganglion cell (RGC) neurons must decide whether to cross or avoid the midline at the optic chiasm to project to targets on both sides of the brain. By combining genetic analyses with in vitro assays, we show that neuropilin 1 (NRP1) promotes contralateral RGC projection in mammals. Unexpectedly, the NRP1 ligand involved is not an axon guidance cue of the class 3 semaphorin family, but VEGF164, the neuropilin-binding isoform of the classical vascular growth factor VEGF-A. VEGF164 is expressed at the chiasm midline and is required for normal contralateral growth in vivo. In outgrowth and growth cone turning assays, VEGF164 acts directly on NRP1-expressing contralateral RGCs to provide growth-promoting and chemoattractive signals. These findings have identified a permissive midline signal for axons at the chiasm midline and provide in vivo evidence that VEGF-A is an essential axon guidance cue.

Highlights

► NRP1 is expressed by contralateral mouse retinal ganglion cell axons ► NRP1 promotes commissural axon crossing at the optic chiasm as a VEGF164 receptor ► VEGF164 acts directly on retinal growth cones as an attractive guidance signal ► VEGF164 and NRP1 are essential for normal contralateral axon growth in vivo

Cited by (0)

4

Present address: Centre for Cancer Biology, Department of Human Immunology, SA Pathology, Adelaide, SA 5000, Australia

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Present address: UCL Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK