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 Blood, 29 January 2009, Vol. 113, No. 5, pp. 1192-1199.
Prepublished online as a Blood First Edition Paper on August 22, 2008; DOI 10.1182/blood-2008-06-162156.

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VASCULAR BIOLOGY

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

Chang Z. Chun1,*, Sukhbir Kaur2,*, Ganesh V. Samant1, Ling Wang3, Kallal Pramanik1, Maija K. Garnaas1, Keguo Li1, Lyndsay Field4, Debabrata Mukhopadhyay3, and Ramani Ramchandran1

1 Department of Pediatrics, CRI Developmental Vascular Biology Program, Translational and Biomedical Research Center, Medical College of Wisconsin, Milwaukee; 2 Genome Technology Branch, National Human Genome Research Institute (NHGRI), National Institutes of Health, Bethesda, MD; 3 Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN; and 4 The University of Massachusetts Dartmouth, North Dartmouth

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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Related Article in Blood Online:

The hunting of the Snrk
Jack L. Arbiser and Levi Fried
Blood 2009 113: 983-984. [Full Text] [PDF]





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