Submitted June 11, 2008
Accepted July 25, 2008
Snrk-1 is involved in multiple steps of angioblast development and acts via notch signaling pathway in artery-vein specification in vertebrates
Chang Z Chun, Sukhbir Kaur, Ganesh V Samant, Ling Wang, Kallal Pramanik, Maija K Garnaas, Keguo Li, Lyndsay Field, Debabrata Mukhopadhyay, and Ramani Ramchandran*
Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States
Genome Technology Branch, NIH, Bethesda, MD, United States
Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, United States
Marine Biology, University of Massachusetts, North Dartmouth, MA, United States
* Corresponding author; email: rramchan{at}mcw.edu.
In vertebrates, molecular mechanisms dictate angioblasts' migration and subsequent differentiation into arteries and veins. In this study, we used a microarray screen to identify a novel member of the sucrose non-fermenting related kinase (snrk-1) family of serine/threonine kinases expressed specifically in the embryonic zebrafish vasculature and investigated its function in vivo. Using gain and loss of function studies in vivo, we show that Snrk-1 plays an essential role in the migration, maintenance and differentiation of angioblasts. The kinase function of Snrk-1 is critical for migration and maintenance, but not for the differentiation of angioblasts. In vitro, snrk-1 knockdown endothelial cells show only defects in migration. The snrk-1 gene acts downstream or parallel to notch and upstream of gridlock during artery-vein specification, and the human gene compensates for zebrafish snrk-1 knockdown, suggesting evolutionary conservation of function.
