CNS-resident progenitors direct the vascularization of neighboring tissues

Matsuoka, R.L., Rossi, A., Stone, O.A., Stainier, D.Y.R.
Proceedings of the National Academy of Sciences of the United States of America   114(38): 10137-10142 (Journal)
Registered Authors
Matsuoka, Ryota, Stainier, Didier
Vegf signaling, angiogenesis, radial glia, spinal cord, zebrafish
MeSH Terms
  • Animals
  • Central Nervous System/cytology
  • Central Nervous System/embryology*
  • Neovascularization, Physiologic/physiology*
  • Neural Stem Cells/cytology
  • Neural Stem Cells/metabolism*
  • Neuroglia/cytology
  • Neuroglia/metabolism
  • Vascular Endothelial Growth Factor Receptor-2/genetics
  • Vascular Endothelial Growth Factor Receptor-2/metabolism
  • Vertebral Artery/cytology
  • Vertebral Artery/embryology*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
28855341 Full text @ Proc. Natl. Acad. Sci. USA
Organ growth requires the coordinated invasion and expansion of blood vessel networks directed by tissue-resident cells and morphogenetic cues. A striking example of this intercellular communication is the vascularization of the central nervous system (CNS), which is driven by neuronal progenitors, including neuroepithelial cells and radial glia. Although the importance of neuronal progenitors in vascular development within the CNS is well recognized, how these progenitors regulate the vasculature outside the CNS remains largely unknown. Here we show that CNS-resident radial glia direct the vascularization of neighboring tissues during development. We find that genetic ablation of radial glia in zebrafish larvae leads to a complete loss of the bilateral vertebral arteries (VTAs) that extend along the ventrolateral sides of the spinal cord. Importantly, VTA formation is not affected by ablation of other CNS cell types, and radial glia ablation also compromises the subsequent formation of the peri-neural vascular plexus (PNVP), a vascular network that surrounds the CNS and is critical for CNS angiogenesis. Mechanistically, we find that radial glia control these processes via Vegfab/Vegfr2 signaling: vegfab is expressed by radial glia, and genetic or pharmacological inhibition of Vegfab/Vegfr2 signaling blocks the formation of the VTAs and subsequently of the PNVP. Moreover, mosaic overexpression of Vegfab in radial glia is sufficient to partially rescue the VTA formation defect in vegfab mutants. Thus, our findings identify a critical function for CNS-resident progenitors in the regulation of vascularization outside the CNS, serving as a paradigm for cross-tissue coordination of vascular morphogenesis and growth.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes