title: The synaptic proteins β-neurexin and neuroligin synergize with extracellular matrix-binding vascular endothelial growth factor a during zebrafish vascular development.
abstract: OBJECTIVE
  The goal of this study was to determine the in vivo functions of the synaptic proteins neurexins and neuroligins in embryonic vascular system development using zebrafish as animal model.
  
  
  RESULTS
  In the present study, we show that the knockdown of the α-form of neurexin 1a induces balance defects and reduced locomotory activity, whereas β-neurexin 1a and neuroligin 1 morphants present defects in sprouting angiogenesis and vascular remodeling, in particular in the caudal plexus and subintestinal vessels. Coinjection of low doses of morpholinos for β-neurexin 1a and neuroligin 1 together or in combination with morpholinos targeting the -heparin--binding isoforms of vascular endothelial growth factor A (encoded by the VEGFAb gene) recapitulates the observed abnormalities, suggesting synergistic activity of these molecules. Similar coinjection experiments with morpholinos, targeting the enzyme heparan sulfate 6-O-sulfotransferase 2, confirm the presence of a functional correlation between extracellular matrix maturation and β-neurexin 1a or neuroligin 1.
  
  
  CONCLUSIONS
  Our data represent the first in vivo evidence of the role of neurexin and neuroligin in embryonic blood vessel formation and provide insights into their mechanism of action.
authors.affiliation: Department of Oncological Sciences, University of Torino Medical School, Candiolo, Italy. alberto.rissone@nih.gov
authors.forename: Alberto
authors.initials: A
authors.lastname: Rissone
authors.forename: Efrem
authors.initials: E
authors.lastname: Foglia
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Sangiorgio
authors.forename: Solei
authors.initials: S
authors.lastname: Cermenati
authors.forename: Stefania
authors.initials: S
authors.lastname: Nicoli
authors.forename: Simona
authors.initials: S
authors.lastname: Cimbro
authors.forename: Monica
authors.initials: M
authors.lastname: Beltrame
authors.forename: Federico
authors.initials: F
authors.lastname: Bussolino
authors.forename: Franco
authors.initials: F
authors.lastname: Cotelli
authors.forename: Marco
authors.initials: M
authors.lastname: Arese
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000196:embryology*; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology; D006023:Glycoproteins / Q000502:physiology*; D006493:Heparin / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D009479:Neuropeptides / Q000502:physiology*; D015238:Sulfotransferases / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D006023:Glycoproteins; D009479:Neuropeptides; D042461:Vascular Endothelial Growth Factor A; C112162:neurexophilin; C093438:neuroligin 1; D006493:Heparin; D015238:Sulfotransferases; C404189:heparan sulfate 6-O-sulfotransferase