ZFIN ID: ZDB-PUB-170111-3
Neuronal sFlt1 and Vegfaa determine venous sprouting and spinal cord vascularization
Wild, R., Klems, A., Takamiya, M., Hayashi, Y., Strähle, U., Ando, K., Mochizuki, N., van Impel, A., Schulte-Merker, S., Krueger, J., Preau, L., le Noble, F.
Date: 2017
Source: Nature communications   8: 13991 (Journal)
Registered Authors: Klems, Alina, le Noble, Ferdinand, Mochizuki, Naoki, Schulte-Merker, Stefan, Strähle, Uwe, Takamiya, Masanari, van Impel, Andreas, Wild, Raphael
Keywords: Angiogenesis, Spinal cord
Microarrays: GEO:GSE89350
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Biomarkers/metabolism
  • Embryo, Nonmammalian/cytology
  • Endothelial Cells/metabolism
  • Endothelial Cells/physiology
  • Gene Expression Regulation, Developmental
  • Mutation
  • Neovascularization, Physiologic
  • Neurons/physiology*
  • Receptors, Notch/genetics
  • Receptors, Notch/metabolism
  • Spinal Cord/blood supply
  • Spinal Cord/embryology*
  • 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*
  • Veins/embryology*
  • Veins/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 28071661 Full text @ Nat. Commun.
Formation of organ-specific vasculatures requires cross-talk between developing tissue and specialized endothelial cells. Here we show how developing zebrafish spinal cord neurons coordinate vessel growth through balancing of neuron-derived Vegfaa, with neuronal sFlt1 restricting Vegfaa-Kdrl mediated angiogenesis at the neurovascular interface. Neuron-specific loss of flt1 or increased neuronal vegfaa expression promotes angiogenesis and peri-neural tube vascular network formation. Combining loss of neuronal flt1 with gain of vegfaa promotes sprout invasion into the neural tube. On loss of neuronal flt1, ectopic sprouts emanate from veins involving special angiogenic cell behaviours including nuclear positioning and a molecular signature distinct from primary arterial or secondary venous sprouting. Manipulation of arteriovenous identity or Notch signalling established that ectopic sprouting in flt1 mutants requires venous endothelium. Conceptually, our data suggest that spinal cord vascularization proceeds from veins involving two-tiered regulation of neuronal sFlt1 and Vegfaa via a novel sprouting mode.