Snrk-1 is involved in multiple steps of angioblast development and acts via notch signaling pathway in artery-vein specification in vertebrates
Chang Z Chun, Sukhbir Kaur, Ganesh V Samant, Ling Wang, Kallal Pramanik, Maija K Garnaas, Keguo Li, Lyndsay Field, Debabrata Mukhopadhyay and Ramani Ramchandran
Prepublished online Aug 22, 2008; doi:10.1182/blood-2008-06-162156
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 non-fermenting 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.
From the discussion :
Angioblasts require specific molecular cues to target them to the midline, and during migration, they must maintain enough numbers to develop into a mature vessel. Our study implies that Snrk-1 plays a critical role in two steps in this process. In the first step where specified angioblasts migrate to the midline, Snrk-1 and its kinase activity are important for angioblast maintenance and migration. In the second step of angioblast specification to arteries or veins, snrk-1 works upstream of grl and downstream or parallel to notch in the signaling cascade involved in A/V specification. Whether snrk-1 performs similar functions in mammalian development is not known and is currently under active investigation.
