title: Arteries are formed by vein-derived endothelial tip cells.
abstract: Tissue vascularization entails the formation of a blood vessel plexus, which remodels into arteries and veins. Here we show, by using time-lapse imaging of zebrafish fin regeneration and genetic lineage tracing of endothelial cells in the mouse retina, that vein-derived endothelial tip cells contribute to emerging arteries. Our movies uncover that arterial-fated tip cells change migration direction and migrate backwards within the expanding vascular plexus. This behaviour critically depends on chemokine receptor cxcr4a function. We show that the relevant Cxcr4a ligand Cxcl12a selectively accumulates in newly forming bone tissue even when ubiquitously overexpressed, pointing towards a tissue-intrinsic mode of chemokine gradient formation. Furthermore, we find that cxcr4a mutant cells can contribute to developing arteries when in association with wild-type cells, suggesting collective migration of endothelial cells. Together, our findings reveal specific cell migratory behaviours in the developing blood vessel plexus and uncover a conserved mode of artery formation.
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Roentgenstr. 20, 48149 Muenster, Germany.
authors.forename: Cong
authors.initials: C
authors.lastname: Xu
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Roentgenstr. 20, 48149 Muenster, Germany.
authors.forename: Sana S
authors.initials: SS
authors.lastname: Hasan
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Roentgenstr. 20, 48149 Muenster, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Schmidt
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Roentgenstr. 20, 48149 Muenster, Germany.
authors.forename: Susana F
authors.initials: SF
authors.lastname: Rocha
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Roentgenstr. 20, 48149 Muenster, Germany.
authors.forename: Mara E
authors.initials: ME
authors.lastname: Pitulescu
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Roentgenstr. 20, 48149 Muenster, Germany.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Bussmann
authors.affiliation: Institute of Cell Biology, ZMBE, Von-Esmarch-Str. 56, 48149 Muenster, Germany.
authors.forename: Dana
authors.initials: D
authors.lastname: Meyen
authors.affiliation: Institute of Cell Biology, ZMBE, Von-Esmarch-Str. 56, 48149 Muenster, Germany.
authors.forename: Erez
authors.initials: E
authors.lastname: Raz
authors.affiliation: 1] Max Planck Institute for Molecular Biomedicine, Roentgenstr. 20, 48149 Muenster, Germany [2] University of Münster, Faculty of Medicine, D-48149 Münster, Germany.
authors.forename: Ralf H
authors.initials: RH
authors.lastname: Adams
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Roentgenstr. 20, 48149 Muenster, Germany.
authors.forename: Arndt F
authors.initials: AF
authors.lastname: Siekmann
mesh_terms: D058500:Animal Fins / Q000098:blood supply / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001158:Arteries / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D019070:Cell Lineage / Q000235:genetics; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018919:Neovascularization, Physiologic; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D015398:Signal Transduction; D059008:Time-Lapse Imaging; D014680:Veins / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D014741:Video Recording; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C514936:CXCR4 protein, mouse; C532358:CXCR4a protein, zebrafish; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D029961:Zebrafish Proteins