Objective — The goal of this study was to determine the in vivo functions of the synaptic molecules Neurexins and Neuroligins in embryonic vascular system development using zebrafish as animal model. Methods and Results — In the present study we show that the knockdown of α-forms of Neurexin 1a induces balance defects and a reduced locomotory activity, while β-Neurexin 1a and Neuroligin1 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 coinjection with VEGFAb morpholino recapitulates the observed abnormalities, suggesting a synergistic activity of these molecules. Similar coinjection experiments with Heparan Sulfate 6-O-Sulfotransferase 2 MO confirm the presence of a genetic interaction between β-Neurexin 1a or Neuroligin 1 and the most extracellular matrix-dependent VEGFA isoforms. Finally we show that the down-regulation of β-Neurexin 1a specifically induces an increase in VEGFAb expression level. Conclusion — Our data represent the first in vivo evidence of the role of Neurexin and Neuroligin in embryonic blood vessels formation providing insights into their mechanism of action.
The synaptic proteins &[beta]-Neurexin and Neuroligin synergize withECM-binding VEGFA during zebrafish vascular development
RISSONE, ALBERTO;BUSSOLINO, Federico;ARESE, Marco
2012-01-01
Abstract
Objective — The goal of this study was to determine the in vivo functions of the synaptic molecules Neurexins and Neuroligins in embryonic vascular system development using zebrafish as animal model. Methods and Results — In the present study we show that the knockdown of α-forms of Neurexin 1a induces balance defects and a reduced locomotory activity, while β-Neurexin 1a and Neuroligin1 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 coinjection with VEGFAb morpholino recapitulates the observed abnormalities, suggesting a synergistic activity of these molecules. Similar coinjection experiments with Heparan Sulfate 6-O-Sulfotransferase 2 MO confirm the presence of a genetic interaction between β-Neurexin 1a or Neuroligin 1 and the most extracellular matrix-dependent VEGFA isoforms. Finally we show that the down-regulation of β-Neurexin 1a specifically induces an increase in VEGFAb expression level. Conclusion — Our data represent the first in vivo evidence of the role of Neurexin and Neuroligin in embryonic blood vessels formation providing insights into their mechanism of action.
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