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(Circulation Research. 2008;103:710.)
© 2008 American Heart Association, Inc.

Molecular Medicine

Syx, a RhoA Guanine Exchange Factor, Is Essential for Angiogenesis In Vivo

Maija K. Garnaas, Karen L. Moodie, Miao-liang Liu, Ganesh V. Samant, Keguo Li, Ruth Marx, Jay M. Baraban, Arie Horowitz^*, Ramani Ramchandran^*

From the Department of Pediatrics (M.K.G., G.V.S., K.L., R.R.), Developmental Vascular Biology Program, Translational and Biomedical Research Center, Children’s Research Institute, Medical College of Wisconsin, Milwaukee; Department of Medicine, Angiogenesis Research Center, Dartmouth Medical School (K.L.M., M.-l.L., A.H.), Lebanon, NH; and Solomon H. Snyder Department of Neuroscience (R.M., J.M.B.), John Hopkins University, Baltimore, Md.

Correspondence to Ramani Ramchandran, Medical College of Wisconsin, PO Box 26509, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail rramchan{at}mcw.edu

Rho GTPases play an important and versatile role in several biological processes. In this study, we identified the zebrafish ortholog of the mammalian Rho A guanine exchange factor, synectin-binding guanine exchange factor (Syx), and determined its in vivo function in the zebrafish and the mouse. We found that Syx is expressed specifically in the vasculature of these organisms. Loss-of-function studies in the zebrafish and mouse point to a specific role for Syx in angiogenic sprouting in the developing vascular bed. Importantly, vasculogenesis and angioblast differentiation steps were unaffected in syx knockdown zebrafish embryos, and the vascular sprouting defects were partially rescued by the mouse ortholog. Syx knockdown in vitro impairs vascular endothelial growth factor-A–induced endothelial cell migration and angiogenesis. We have also uncovered a potential mechanism of endothelial sprout guidance in which angiomotin, a component of endothelial cell junctions, plays an additive role with Syx in directing endothelial sprouts. These results identify Syx as an essential contributor to angiogenesis in vivo.

Key Words: vascular • zebrafish • PDZ • knockdown • intersomitic vessels

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