title: The hormonal peptide Elabela guides angioblasts to the midline during vasculogenesis.
abstract: A key step in the de novo formation of the embryonic vasculature is the migration of endothelial precursors, the angioblasts, to the position of the future vessels. To form the first axial vessels, angioblasts migrate towards the midline and coalesce underneath the notochord. Vascular endothelial growth factor has been proposed to serve as a chemoattractant for the angioblasts and to regulate this medial migration. Here we challenge this model and instead demonstrate that angioblasts rely on their intrinsic expression of Apelin receptors (Aplr, APJ) for their migration to the midline. We further show that during this angioblast migration Apelin receptor signaling is mainly triggered by the recently discovered ligand Elabela (Ela). As neither of the ligands Ela or Apelin (Apln) nor their receptors have previously been implicated in regulating angioblast migration, we hereby provide a novel mechanism for regulating vasculogenesis, with direct relevance to physiological and pathological angiogenesis.
authors.affiliation: University of Muenster, Muenster, Germany.
authors.forename: Christian S M
authors.initials: CS
authors.lastname: Helker
authors.affiliation: University of Muenster, Muenster, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Schuermann
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Muenster, Germany.
authors.forename: Cathrin
authors.initials: C
authors.lastname: Pollmann
authors.affiliation: Institute of Medical Biology, Human Genetics and Embryology Laboratory, A*STAR, Singapore, Singapore.
authors.forename: Serene C
authors.initials: SC
authors.lastname: Chng
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Muenster, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Kiefer
authors.affiliation: Institute of Medical Biology, Human Genetics and Embryology Laboratory, A*STAR, Singapore, Singapore.
authors.forename: Bruno
authors.initials: B
authors.lastname: Reversade
authors.affiliation: University of Muenster, Muenster, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Herzog
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D018925:Chemokines / Q000378:metabolism*; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology*; D066026:Endothelial Progenitor Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D008954:Models, Biological; D016296:Mutagenesis; D018919:Neovascularization, Physiologic / Q000502:physiology*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: C000595490:Apela protein, zebrafish; D018925:Chemokines; D017931:DNA Primers; D029961:Zebrafish Proteins; C519092:apln protein, zebrafish
keywords: Vegf; angioblast migration; chemoattractant; developmental biology; dorsal aorta; endothelial cell migration; human biology; medicine; notochord; stem cells; zebrafish