Arterial and Venous Progenitors of the Major Axial Vessels Originate at Distinct Locations

• Published in: Developmental cell 2013-04, Vol.25 (2), p.196-206
• Main Authors: Kohli, Vikram, Schumacher, Jennifer A., Desai, Sharina Palencia, Rehn, Kira, Sumanas, Saulius
• Format: Article
• Language: English
• Subjects: Animals; Arteries - cytology; Arteries - metabolism; Cell Differentiation; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - metabolism; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Gene Expression Regulation, Developmental; Hedgehog Proteins - genetics; Hedgehog Proteins - metabolism; In Situ Hybridization; Neovascularization, Physiologic; Signal Transduction; Stem Cells - cytology; Stem Cells - metabolism; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Veins - cytology; Veins - metabolism; Zebrafish - genetics; Zebrafish - growth & development; Zebrafish - metabolism; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2013.03.017

Currently, it remains controversial how vascular endothelial progenitor cells (angioblasts) establish their arterial or venous fates. We show using zebrafish that the arterial progenitors of the major axial vessels originate earlier and closer to the midline than the venous progenitors. Both medial and lateral progenitor populations migrate to distinct arterial and venous positions and not into a common precursor vessel as previously suggested. Overexpression of VEGF or Hedgehog (Hh) homologs results in the partially randomized distribution of arterial and venous progenitors within the axial vessels. We further demonstrate that the function of the Etv2 transcription factor is required at earlier stages for arterial development than for venous. Our results argue that the medial angioblasts undergo arterial differentiation because they receive higher concentration of Vegf and Hh morphogens than the lateral angioblasts. We propose a revised model of arterial-venous differentiation that explains how angioblasts choose between an arterial and venous fate. [Display omitted] •Two endothelial progenitor populations originate in the lateral plate mesoderm•Medial cells contribute to the artery, while lateral cells contribute to the vein•VegfA and Hh concentrations control the distribution of medial and lateral cells•Etv2 function is required earlier for arterial specification than for venous How do endothelial progenitors choose between arterial and venous fates? Kohli, Schumacher et al. show that, in zebrafish, arterial and venous progenitors of the axial vessels originate at distinct locations that experience different Hh and VEGF concentrations. The transcription factor Etv2 is required at distinct time points in each population.