Motor neurons control blood vessel patterning in the developing spinal cord

Nat Commun. 2017 Mar 6;8:14583. doi: 10.1038/ncomms14583.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autocrine Communication
  • Blood Vessels / growth & development
  • Blood Vessels / metabolism*
  • Body Patterning / genetics
  • Chickens
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Neurons / cytology
  • Motor Neurons / metabolism*
  • Neovascularization, Physiologic / genetics*
  • Neuropilin-1 / genetics
  • Neuropilin-1 / metabolism
  • Signal Transduction
  • Spinal Cord / blood supply
  • Spinal Cord / growth & development
  • Spinal Cord / metabolism*
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-1 / genetics*
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism

Substances

  • Vascular Endothelial Growth Factor A
  • enhanced green fluorescent protein
  • vascular endothelial growth factor A, mouse
  • Neuropilin-1
  • Green Fluorescent Proteins
  • Flt1 protein, mouse
  • Vascular Endothelial Growth Factor Receptor-1