Vascular endothelial growth factor signaling regulates the segregation of artery and vein via ERK activity during vascular development

Se Hee Kim, Christopher E. Schmitt, Melissa J. Woolls, Melinda B. Holland, Jun Dae Kim, Suk Won Jin

Research output: Contribution to journalArticle

10 Scopus citations

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 (PI3. K), 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.

Original languageEnglish (US)
Pages (from-to)1212-1216
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume430
Issue number4
DOIs
StatePublished - Jan 25 2013

Keywords

  • Axial vessel
  • Erk
  • Vascular development
  • Vegf-A
  • Zebrafish

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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