The synaptic proteins ß-neurexin and neuroligin synergize with extracellular matrix-binding vascular endothelial growth factor a during zebrafish vascular development.
Arterioscler Thromb Vasc Biol
; 32(7): 1563-72, 2012 Jul.
Article
em En
| MEDLINE
| ID: mdl-22516065
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. METHODS ANDRESULTS:
In the present study, we show that the knockdown of the α-form of neurexin 1a induces balance defects and reduced locomotory activity, whereas ß-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 ß-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 ß-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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vasos Sanguíneos
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Neuropeptídeos
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Peixe-Zebra
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Glicoproteínas
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Heparina
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Moléculas de Adesão Celular Neuronais
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Neovascularização Fisiológica
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Fator A de Crescimento do Endotélio Vascular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Itália