VEGF-A and Neuropilin 1 (NRP1) shape axon projections in the developing CNS via dual roles in neurons and blood vessels

Lynda Erskine, Urielle Francois, Laura Denti, Andy Joyce, Miguel Tillo, Freyja Bruce, Neil Vargesson, Christiana Ruhrberg

Research output: Contribution to journalArticle

12 Citations (Scopus)
8 Downloads (Pure)

Abstract

Visual information is relayed from the eye to the brain via retinal ganglion cell (RGC) axons. Mice lacking NRP1 or NRP1-binding VEGF-A isoforms have defective RGC axon organisation alongside brain vascular defects. It is not known whether axonal defects are caused exclusively by defective VEGF-A signalling in RGCs or are exacerbated by abnormal vascular morphology. Targeted NRP1 ablation in RGCs with a Brn3bCre knock-in allele reduced axonal midline crossing at the optic chiasm and optic tract fasciculation. In contrast, Tie2-Cre-mediated endothelial NRP1 ablation induced axon exclusion zones in the optic tracts without impairing axon crossing. Similar defects were observed in Vegfa120/120 and Vegfa188/188 mice, which have vascular defects as a result of their expression of single VEGF-A isoforms. Ectopic midline vascularisation in endothelial Nrp1 and Vegfa188/188 mutants caused additional axonal exclusion zones within the chiasm. As in vitro and in vivo assays demonstrated that vessels do not repel axons, abnormally large or ectopically positioned vessels are likely to present physical obstacles to axon growth. We conclude that proper axonal wiring during brain development depends on the precise molecular control of neurovascular co-patterning.
Original languageEnglish
Pages (from-to)2504-2516
Number of pages13
JournalDevelopment
Volume144
Issue number13
Early online date4 Jul 2017
DOIs
Publication statusPublished - Jul 2017

Keywords

  • retinal ganglion cell
  • optic chiasm
  • blood vessel
  • axon guidance
  • VEGF-A

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