VEGF-A and neuropilin 1 (NRP1) shape axon projections in the developing CNS via dual roles in neurons and blood vessels
- Resource Type
- Authors
- Miguel Tillo; Urielle François; Laura Denti; Neil Vargesson; Freyja Bruce; Christiana Ruhrberg; Andy Joyce; Lynda Erskine
- Source
- BASE-Bielefeld Academic Search Engine
Development (Cambridge, England)
- Subject
- Central Nervous System
Retinal Ganglion Cells
Vascular Endothelial Growth Factor A
0301 basic medicine
genetic structures
Optic tract
Neovascularization, Physiologic
Optic chiasm
Biology
VEGF-A
03 medical and health sciences
Neuropilin 1
medicine
Neuropilin
Animals
Visual Pathways
Retinal ganglion cell
Diencephalon
Axon
Molecular Biology
Body Patterning
Homeodomain Proteins
Axon guidance
Endothelial Cells
Anatomy
Axons
Neuropilin-1
Transcription Factor Brn-3B
eye diseases
Cell biology
Mice, Inbred C57BL
Vascular endothelial growth factor A
030104 developmental biology
medicine.anatomical_structure
nervous system
Gene Knockdown Techniques
Mutation
Blood Vessels
Blood vessel
sense organs
Research Article
Developmental Biology
- Language
- ISSN
- 1477-9129
0950-1991
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.
Summary: NRP1 plays a dual role in retinal ganglion cells and in vascular endothelial cells to organise axons along the optic pathway between the mouse retina and diencephalon.