Snrk-1 is involved in multiple steps of angioblast development and acts via notch signaling pathway in artery-vein specification in vertebrates.
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.
Chun
Chang Z
CZ
Department of Pediatrics, CRI Developmental Vascular Biology Program, Translational and Biomedical Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Kaur
Sukhbir
S
Samant
Ganesh V
GV
Wang
Ling
L
Pramanik
Kallal
K
Garnaas
Maija K
MK
Li
Keguo
K
Field
Lyndsay
L
Mukhopadhyay
Debabrata
D
Ramchandran
Ramani
R
D000818:Animals; D001158:Arteries / Q000196:embryology*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D042783:Endothelial Cells / Q000201:enzymology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D014680:Veins / Q000196:embryology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D017346:Protein Serine-Threonine Kinases; D051880:Receptors, Notch; D029961:Zebrafish Proteins; C405954:hey2 protein, zebrafish; C071570:SNF1-related protein kinases