title: Vascular endothelial growth factor signaling regulates the segregation of artery and vein via ERK activity during vascular development.
abstract: Segregation of two axial vessels, the dorsal aorta and caudal vein, is one of the earliest patterning events occur during development of vasculature. Despite the importance of this process and recent advances in our understanding on vascular patterning during development, molecular mechanisms that coordinate the segregation of axial vessels remain largely elusive. In this report, we find that vascular endothelial growth factor-A (Vegf-A) signaling regulates the segregation of dorsal aorta and axial vein during development. Inhibition of Vegf-A pathway components including ligand Vegf-A and its cognate receptor Kdrl, caused failure in segregation of axial vessels in zebrafish embryos. Similarly, chemical inhibition of Mitogen-activated protein kinase kinase (Map2k1)/Extracellular-signal-regulated kinases (Erk) and phosphatidylinositol 3-kinases (PI3K), which are downstream effectors of Vegf-A signaling pathway, led to the fusion of two axial vessels. Moreover, we find that restoring Erk activity by over-expression of constitutively active MEK in embryos with a reduced level of Vegf-A signaling can rescue the defects in axial vessel segregation. Taken together, our data show that segregation of axial vessels requires the function of Vegf-A signaling, and Erk may function as the major downstream effector in this process.
authors.affiliation: McAllister Heart Institute, Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Se-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Schmitt
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Woolls
authors.forename: Melinda B
authors.initials: MB
authors.lastname: Holland
authors.forename: Jun-Dae
authors.initials: JD
authors.lastname: Kim
authors.forename: Suk-Won
authors.initials: SW
authors.lastname: Jin
mesh_terms: D000818:Animals; D001011:Aorta / Q000254:growth & development*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000502:physiology*; D014680:Veins / Q000254:growth & development*; D015027:Zebrafish / Q000254:growth & development
chemical_list: D042461:Vascular Endothelial Growth Factor A; D048049:Extracellular Signal-Regulated MAP Kinases