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Radial glia regulate vascular patterning around the developing spinal cord

Matsuoka, Ryota L, Marass, Michele, Avdesh, Avdesh, Helker, Christian SM, Maischein, Hans-Martin, Grosse, Ann S, Kaur, Harmandeep, Lawson, Nathan D +2 more·2016·eLife

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.

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Cited by

Sorted by citations

Authors
Matsuoka, R. L., Marass, M., Avdesh, A., Helker, C. S., Maischein, H.-M., Grosse, A. S., Kaur, H., Lawson, N. D., Herzog, W., & Stainier, D. Y.
Venue
eLife
Published
2016-11-17
Volume
5
ISSN
2050-084X
Cited by
90
References
3
Language
en
Funders
  • Human Frontier Science Program (LT001023/2012-L)
  • Japan Society for the Promotion of Science
  • Damon Runyon Cancer Research Foundation (DRG#2104-12)
  • Excellence Cluster Cardio-Pulmonary System
  • German Centre for Cardiovascular Research
  • Max-Planck-Gesellschaft
  • National Institutes of Health (HL54737)
  • David and Lucile Packard Foundation

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