Journal
BLOOD
Volume 113, Issue 5, Pages 1192-1199Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-06-162156
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Funding
- National Institutes of Health [HL072178, HL70567]
- Medical College of Wisconsin, Milwaukee
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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 nonfermenting 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 down-stream 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. (Blood. 2009; 113: 1192-1199)
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