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      Snrk-1 is involved in multiple steps of angioblast development and acts via notch signaling pathway in artery-vein specification in vertebrates.

      Blood
      Animals, Arteries, embryology, Basic Helix-Loop-Helix Transcription Factors, genetics, metabolism, Cell Movement, physiology, Endothelial Cells, enzymology, Gene Expression Regulation, Developmental, Gene Expression Regulation, Enzymologic, Gene Knockdown Techniques, Humans, Oligonucleotide Array Sequence Analysis, Protein-Serine-Threonine Kinases, biosynthesis, Receptors, Notch, Veins, Zebrafish, Zebrafish Proteins

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          Abstract

          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 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.

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