title: Radial glia regulate vascular patterning around the developing spinal cord.
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:sflt1mutants 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.
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
authors.forename: Ryota L
authors.initials: RL
authors.lastname: Matsuoka
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
authors.forename: Michele
authors.initials: M
authors.lastname: Marass
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
authors.forename: Avdesh
authors.initials: A
authors.lastname: Avdesh
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
authors.forename: Christian Sm
authors.initials: CS
authors.lastname: Helker
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Maischein
authors.affiliation: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States.
authors.forename: Ann S
authors.initials: AS
authors.lastname: Grosse
authors.affiliation: Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
authors.forename: Harmandeep
authors.initials: H
authors.lastname: Kaur
authors.affiliation: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Lawson
authors.affiliation: Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster, Germany.|Max Planck Institute for Molecular Biomedicine, Muenster, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Herzog
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
authors.forename: Didier Yr
authors.identifier: http://orcid.org/0000-0002-0382-0026
authors.initials: DY
authors.lastname: Stainier
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000254:growth & development / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D009030:Mosaicism; D058953:Neural Stem Cells / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D013116:Spinal Cord / Q000098:blood supply / Q000254:growth & development / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A; C583604:Vegfaa protein, zebrafish; D029961:Zebrafish Proteins; C583603:FLT1 protein, zebrafish; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: angiogenic regulation; developmental biology; neuroscience; radial glia; spinal cord; stem cells; vascular patterning; zebrafish