Abstract
Formation of a precise vascular network within the central nervous system is of critical importance to assure delivery of oxygen and nutrients and for accurate functionality of neuronal networks. Vascularization of the spinal cord is a highly stereotypical process. However, the guidance cues controlling blood vessel patterning in this organ remain largely unknown. Here we describe a new neuro-vascular communication mechanism that controls vessel guidance in the developing spinal cord. We show that motor neuron columns remain avascular during a developmental time window, despite expressing high levels of the pro-angiogenic vascular endothelial growth factor (VEGF). We describe that motor neurons express the VEGF trapping receptor sFlt1 via a Neuropilin-1-dependent mechanism. Using a VEGF gain-of-function approach in mice and a motor neuron-specific sFlt1 loss-of-function approach in chicken, we show that motor neurons control blood vessel patterning by an autocrine mechanism that titrates motor neuron-derived VEGF via their own expression of sFlt1.
Highlights
Formation of a precise vascular network within the central nervous system is of critical importance to assure delivery of oxygen and nutrients and for accurate functionality of neuronal networks
These previous findings raise the questions of what neuronal cell types are permissive for blood vessel sprouting from the perineural vascular plexus (PNVP)? When do motor neurons (MNs) columns become vascularized in development? And how are vascular endothelial growth factor (VEGF) expression and signalling regulated by the neuronal compartment to control the stereotypical blood vessel patterning in the spinal cord (SC)? Here we have revisited those initial findings and answered these questions
These results suggest that the ventral domains of floor plate, p3, V3 interneurons, pMN and MNs might control the initial steps of SC vascularization and patterning, with V3 interneurons, p3 and pMN neuronal domains acting as ‘vascular attractant’ sites, whereas floor plate and MNs acting as ‘repellent’ sites
Summary
Formation of a precise vascular network within the central nervous system is of critical importance to assure delivery of oxygen and nutrients and for accurate functionality of neuronal networks. The identity of the neural cells, the spatial cues and the signalling mechanisms that regulate this process remain largely unknown It is unclear whether patterning cues modulate VEGF signalling or act independently of the VEGF axis. When blood vessel sprouts invade the SC from the ventral side they avoid the floor plate and the motor neurons (MNs), despite the fact that VEGF is expressed in those areas[26,27]. These previous findings raise the questions of what neuronal cell types are permissive for blood vessel sprouting from the PNVP? These previous findings raise the questions of what neuronal cell types are permissive for blood vessel sprouting from the PNVP? When do MN columns become vascularized in development? And how are VEGF expression and signalling regulated by the neuronal compartment to control the stereotypical blood vessel patterning in the SC? Here we have revisited those initial findings and answered these questions
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