Neuronal sFlt1 and Vegfaa determine venous sprouting and spinal cord vascularization

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DOI

  • Raphael Wild, Karlsruhe Institute of Technology (KIT), Germany
  • Alina Klems, Karlsruhe Institute of Technology (KIT), Germany
  • Masanari Takamiya, Karlsruhe Institute of Technology (KIT), Germany
  • Yuya Hayashi
  • Uwe Strähle, Karlsruhe Institute of Technology (KIT), Germany
  • Koji Ando, National Cerebral and Cardiovascular Research Institute, Japan
  • Naoki Mochizuki, National Cerebral and Cardiovascular Research Institute, Japan
  • Andreas van Impel, University of Münster, Germany
  • Stefan Schulte-Merker, University of Münster, Germany
  • Janna Krueger, Sunnybrook Research Institute, Canada
  • Laetitia Preau, Karlsruhe Institute of Technology (KIT), Germany
  • Ferdinand le Noble, Karlsruhe Institute of Technology (KIT), Germany
Formation of organ-specific vasculatures requires cross-talk between developing tissue and specialized endothelial cells. Here we show how developing zebrafish spinal cord neurons coordinate vessel growth through balancing of neuron-derived Vegfaa, with neuronal sFlt1 restricting Vegfaa-Kdrl mediated angiogenesis at the neurovascular interface. Neuron-specific loss of flt1 or increased neuronal vegfaa expression promotes angiogenesis and peri-neural tube vascular network formation. Combining loss of neuronal flt1 with gain of vegfaa promotes sprout invasion into the neural tube. On loss of neuronal flt1, ectopic sprouts emanate from veins involving special angiogenic cell behaviours including nuclear positioning and a molecular signature distinct from primary arterial or secondary venous sprouting. Manipulation of arteriovenous identity or Notch signalling established that ectopic sprouting in flt1 mutants requires venous endothelium. Conceptually, our data suggest that spinal cord vascularization proceeds from veins involving two-tiered regulation of neuronal sFlt1 and Vegfaa via a novel sprouting mode.
Original languageEnglish
Article number13991
JournalNature Communications
Volume8
Number of pages17
ISSN2041-1723
DOIs
Publication statusPublished - 10 Jan 2017

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