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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
Authors:Chun Chang Z  Kaur Sukhbir  Samant Ganesh V  Wang Ling  Pramanik Kallal  Garnaas Maija K  Li Keguo  Field Lyndsay  Mukhopadhyay Debabrata  Ramchandran Ramani
Affiliation:Department of Pediatrics, CRI Developmental Vascular Biology Program, Translational and Biomedical Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
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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