Genetic evidence for a noncanonical function of seryl-tRNA synthetase in vascular development.
In a recent genetic screen, we identified mutations in genes important for vascular development and maintenance in zebrafish (Jin et al. Dev Biol. 2007;307:29-42). Mutations [corrected] at the adrasteia (adr) locus cause a pronounced dilatation of the aortic arch vessels as well as aberrant patterning of the hindbrain capillaries and, to a lesser extent, intersomitic vessels. This dilatation of the aortic arch vessels does not appear to be caused by increased cell proliferation but is dependent on vascular endothelial growth factor (Vegf) signaling. By positional cloning, we isolated seryl-tRNA synthetase (sars) as the gene affected by the adr mutations. Small interfering RNA knockdown experiments in human umbilical vein endothelial cell cultures indicate that SARS also regulates endothelial sprouting. These analyses of zebrafish and human endothelial cells reveal a new noncanonical function of Sars in endothelial development.
Department of Biochemistry and Biophysics and the Cardiovascular Research Institute, Programs in Developmental Biology, Genetics, and Human Genetics, University of California, San Francisco, San Francisco, CA 94158, USA.
Wiebke
W
Herzog
Katja
K
Müller
Jan
J
Huisken
Didier Y R
DY
Stainier
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000196:embryology / Q000502:physiology; D001921:Brain / Q000502:physiology; D002455:Cell Division; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002874:Chromosome Mapping; D003513:Cycloheximide / Q000494:pharmacology; D004625:Embryo, Nonmammalian / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D006321:Heart / Q000196:embryology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology; D011758:Pyrroles / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D012714:Serine-tRNA Ligase / Q000235:genetics*; D014162:Transfection; D014471:Umbilical Veins / Q000166:cytology / Q000502:physiology; D015027:Zebrafish
D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; D034741:RNA, Small Interfering; C116890:Semaxinib; D003513:Cycloheximide; D012714:Serine-tRNA Ligase