Arteries are formed by vein-derived endothelial tip cells
Cong Xu, Sana Hasan, Inga Schmidt, Susana F. Rocha, Jeroen Bussmann, Ralf
H. Adams and Arndt F. Siekmann*
*Max Planck Institute for Molecular Biomedicine, Roentgenstr. 20, 48149
Muenster, Germany
Tissue vascularization entails the formation of a blood vessel plexus, which
subsequently remodels into a hierarchical network consisting of arteries and veins.
Using time-lapse imaging of zebrafish fin regeneration and genetic lineage tracing
of endothelial cells in the mouse retina, we show that vein-derived endothelial tip
cells contribute to emerging arteries. By contrast, we did not detect arterial cell
contribution to forming veins. Our time-lapse movies uncover that arterial-fated tip
cells changed direction and migrated against the outgrowing vasculature. In
animals mutant for the chemokine receptor cxcr4a, endothelial cell turning and
thus artery formation was specifically affected. Through cell transplantation
experiments, we found that cxcr4a mutant cells could contribute to developing
arteries when in association with wildtype cells, suggesting collective migration of
endothelial cells during artery formation. Together, our findings reveal specific cell
migratory behaviors in the developing blood vessel plexus, and uncover a
conserved mode of artery formation.