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Neuronal sFlt1 and Vegfaa determine venous sprouting and spinal cord vascularization

Wild, Raphael; Klems, Alina; Takamiya, Masanari; Hayashi, Yuya; Strähle, Uwe; Ando, Koji; Mochizuki, Naoki; van Impel, Andreas; Schulte-Merker, Stefan; Krueger, Janna; Preau, Laetitia; le Noble, Ferdinand



Abstract (englisch): 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.


Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Zoologisches Institut (ZOO)
Publikationstyp Zeitschriftenaufsatz
Jahr 2017
Sprache Englisch
Identifikator DOI: 10.1038/ncomms13991
ISSN: 2041-1723
URN: urn:nbn:de:swb:90-653033
KITopen ID: 1000065303
HGF-Programm 47.01.01; LK 01
Erschienen in Nature Communications
Band 8
Seiten 13991
Lizenz CC BY 4.0: Creative Commons Namensnennung 4.0 International
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
Schlagworte Angiogenesis, Spinal cord
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