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

Blood. 2009 Jan 29;113(5):1192-9. doi: 10.1182/blood-2008-06-162156. Epub 2008 Aug 22.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Receptors, Notch
  • Zebrafish Proteins
  • hey2 protein, zebrafish
  • SNF1-related protein kinases
  • Protein Serine-Threonine Kinases