Radial glia regulate vascular patterning around the developing spinal cord

Elife. 2016 Nov 17:5:e20253. doi: 10.7554/eLife.20253.

Abstract

Vascular networks surrounding individual organs are important for their development, maintenance, and function; however, how these networks are assembled remains poorly understood. Here we show that CNS progenitors, referred to as radial glia, modulate vascular patterning around the spinal cord by acting as negative regulators. We found that radial glia ablation in zebrafish embryos leads to excessive sprouting of the trunk vessels around the spinal cord, and exclusively those of venous identity. Mechanistically, we determined that radial glia control this process via the Vegf decoy receptor sFlt1: sflt1 mutants exhibit the venous over-sprouting observed in radial glia-ablated larvae, and sFlt1 overexpression rescues it. Genetic mosaic analyses show that sFlt1 function in trunk endothelial cells can limit their over-sprouting. Together, our findings identify CNS-resident progenitors as critical angiogenic regulators that determine the precise patterning of the vasculature around the spinal cord, providing novel insights into vascular network formation around developing organs.

Keywords: angiogenic regulation; developmental biology; neuroscience; radial glia; spinal cord; stem cells; vascular patterning; zebrafish.

MeSH terms

  • Animals
  • Blood Vessels / growth & development
  • Blood Vessels / metabolism
  • Cell Differentiation / genetics*
  • Endothelial Cells / metabolism
  • Gene Expression Regulation
  • Mosaicism
  • Neural Stem Cells / metabolism
  • Neuroglia / metabolism
  • Organogenesis / genetics*
  • Signal Transduction / genetics
  • Spinal Cord / blood supply
  • Spinal Cord / growth & development
  • Spinal Cord / metabolism*
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor Receptor-1 / genetics*
  • Zebrafish / genetics
  • Zebrafish / growth & development
  • Zebrafish Proteins / genetics*

Substances

  • Vascular Endothelial Growth Factor A
  • Vegfaa protein, zebrafish
  • Zebrafish Proteins
  • FLT1 protein, zebrafish
  • Vascular Endothelial Growth Factor Receptor-1