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(Circulation Research. 2009;104:1260.)
© 2009 American Heart Association, Inc.

Molecular Medicine

Genetic Evidence for a Noncanonical Function of Seryl-tRNA Synthetase in Vascular Development

Wiebke Herzog, Katja Müller, Jan Huisken, Didier Y.R. Stainier

From the 1. Department of Biochemistry and Biophysics and the Cardiovascular Research Institute (W.H., J.H., D.Y.R.S.), Programs in Developmental Biology, Genetics, and Human Genetics, University of California San Francisco, 2. Westphalian Wilhelms University and Max-Planck Institute for Molecular Biomedicine (W.H., K.M.), Muenster, Germany.

Correspondence to Dr Didier Stainier, Professor, Biochemistry and Biophysics, University of California, San Francisco, 1550 4th St, San Francisco, CA 94158. E-mail didier.stainier{at}ucsf.edu

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). Thirty-two mutations 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.

Key Words: seryl-tRNA synthetase • SerRS • zebrafish • angiogenesis • vascular dilatation