1. Radial glia regulate vascular patterning around the developing spinal cord.
- Author
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Matsuoka RL, Marass M, Avdesh A, Helker CS, Maischein HM, Grosse AS, Kaur H, Lawson ND, Herzog W, and Stainier DY
- Subjects
- Animals, Blood Vessels growth & development, Blood Vessels metabolism, Endothelial Cells metabolism, Gene Expression Regulation, Mosaicism, Neural Stem Cells metabolism, Neuroglia metabolism, Signal Transduction genetics, Spinal Cord blood supply, Spinal Cord growth & development, Zebrafish genetics, Zebrafish growth & development, Cell Differentiation genetics, Organogenesis genetics, Spinal Cord metabolism, Vascular Endothelial Growth Factor A genetics, Vascular Endothelial Growth Factor Receptor-1 genetics, Zebrafish Proteins genetics
- 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., Competing Interests: DYRS: Reviewing editor, eLife. The other authors declare that no competing interests exist.
- Published
- 2016
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