Radial glia regulate vascular patterning around the developing spinal cord

  1. Ryota L Matsuoka  Is a corresponding author
  2. Michele Marass
  3. Avdesh Avdesh
  4. Christian SM Helker
  5. Hans-Martin Maischein
  6. Ann S Grosse
  7. Harmandeep Kaur
  8. Nathan D Lawson
  9. Wiebke Herzog
  10. Didier YR Stainier  Is a corresponding author
  1. Max Planck Institute for Heart and Lung Research, Germany
  2. University of Massachusetts Medical School, United States
  3. 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

  1. Ryota L Matsuoka

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    For correspondence
    ryota.matsuoka@mpi-bn.mpg.de
    Competing interests
    No competing interests declared.
  2. Michele Marass

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
  3. Avdesh Avdesh

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
  4. Christian SM Helker

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
  5. Hans-Martin Maischein

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
  6. Ann S Grosse

    Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
  7. Harmandeep Kaur

    Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
  8. Nathan D Lawson

    Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
  9. Wiebke Herzog

    Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster, Germany
    Competing interests
    No competing interests declared.
  10. Didier YR Stainier

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    For correspondence
    Didier.Stainier@mpi-bn.mpg.de
    Competing interests
    Didier YR Stainier, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0382-0026

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.

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).

Reviewing Editor

  1. Marianne Bronner, California Institute of Technology, United States

Publication history

  1. Received: August 2, 2016
  2. Accepted: November 16, 2016
  3. Accepted Manuscript published: November 17, 2016 (version 1)
  4. 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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  1. Ryota L Matsuoka
  2. Michele Marass
  3. Avdesh Avdesh
  4. Christian SM Helker
  5. Hans-Martin Maischein
  6. Ann S Grosse
  7. Harmandeep Kaur
  8. Nathan D Lawson
  9. Wiebke Herzog
  10. Didier YR Stainier
(2016)
Radial glia regulate vascular patterning around the developing spinal cord
eLife 5:e20253.
https://doi.org/10.7554/eLife.20253
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