Radial glia regulate vascular patterning around the developing spinal cord
- Max Planck Institute for Heart and Lung Research, Germany
- University of Massachusetts Medical School, United States
- University of Muenster, Germany
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.
Article and author information
Author details
Didier YR Stainier
Funding
Max-Planck-Gesellschaft
- Didier YR Stainier
National Institutes of Health (HL54737)
- Didier YR Stainier
Human Frontier Science Program (LT001023/2012-L)
- Ryota L Matsuoka
Japan Society for the Promotion of Science
- Ryota L Matsuoka
David and Lucile Packard Foundation
- Didier YR Stainier
Damon Runyon Cancer Research Foundation (DRG#2104-12)
- Ryota L Matsuoka
Deutsches Zentrum für Herz-Kreislauf-Forschung
- Ryota L Matsuoka
Excellence Cluster Cardio-Pulmonary System
- Ryota L Matsuoka
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Marianne Bronner, California Institute of Technology, United States
Ethics
Animal experimentation: This study was performed in strict accordance with institutional (UCSF and MPG) and national ethical and animal welfare guidelines. All of the animals were handled according to approved institutional animal care and protocol (Permission No. B2/1068).
Version history
- Received: August 2, 2016
- Accepted: November 16, 2016
- Accepted Manuscript published: November 17, 2016 (version 1)
- Version of Record published: November 25, 2016 (version 2)
Copyright
© 2016, Matsuoka et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Radial glia regulate vascular patterning around the developing spinal cord
eLife 5:e20253.
https://doi.org/10.7554/eLife.20253
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