VEGF-A and neuropilin 1 (NRP1) shape axon projections in the developing CNS via dual roles in neurons and blood vessels
Development. 2017-07-01; 144(13): 2504-2516
DOI: 10.1242/dev.151621
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1. Development. 2017 Jul 1;144(13):2504-2516. doi: 10.1242/dev.151621.
VEGF-A and neuropilin 1 (NRP1) shape axon projections in the developing CNS via
dual roles in neurons and blood vessels.
Erskine L(1), François U(2), Denti L(3), Joyce A(3), Tillo M(3), Bruce F(2),
Vargesson N(2), Ruhrberg C(4).
Author information:
(1)School of Medicine, Medical Sciences and Nutrition, Institute of Medical
Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK
.
(2)School of Medicine, Medical Sciences and Nutrition, Institute of Medical
Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
(3)UCL Institute of Ophthalmology, University College London, 11-43 Bath Street,
London EC1V 9EL, UK.
(4)UCL Institute of Ophthalmology, University College London, 11-43 Bath Street,
London EC1V 9EL, UK .
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.
© 2017. Published by The Company of Biologists Ltd.
DOI: 10.1242/dev.151621
PMCID: PMC5536872
PMID: 28676569 [Indexed for MEDLINE]
Conflict of interest statement: Competing interestsThe authors declare no
competing or financial interests.