phospholipase C gamma-1 is required downstream of vascular endothelial growth factor during arterial development.
In this study, we utilize transgenic zebrafish with fluorescently labeled blood vessels to identify and characterize a mutant (y10) that displays specific defects in the formation of arteries, but not veins. We find that y10 encodes phospholipase C gamma-1 (plcg1), a known effector of receptor tyrosine kinase signaling. We further show that plcg1y10 mutant embryos fail to respond to exogenous Vegf. Our results indicate that Plcg1 functions specifically downstream of the Vegf receptor during embryonic development to govern formation of the arterial system.
Lawson
Nathan D
ND
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Nathan.Lawson@umassmed.edu
Mugford
Joshua W
JW
Diamond
Brigid A
BA
Weinstein
Brant M
BM
D000818:Animals; D030801:Animals, Genetically Modified; D001158:Arteries / Q000166:cytology / Q000196:embryology*; D001483:Base Sequence; D003433:Crosses, Genetic; D017931:DNA Primers; D004625:Embryo, Nonmammalian / Q000502:physiology; D016228:Endothelial Growth Factors / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006580:Genetic Carrier Screening; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008222:Lymphokines / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000196:embryology; D051966:Phospholipase C gamma; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D010738:Type C Phospholipases / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D015027:Zebrafish / Q000196:embryology*
D017931:DNA Primers; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D010738:Type C Phospholipases; D051966:Phospholipase C gamma