The hormonal peptide Elabela guides angioblasts to the midline during vasculogenesis

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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 (Vegf) 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.

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Christian S M Helker

n/a, University of Muenster, Muenster, Germany

Competing interests
The authors declare that no competing interests exist.
Annika Schuermann

n/a, University of Muenster, Muenster, Germany

Competing interests
The authors declare that no competing interests exist.
Cathrin Pollmann

n/a, Max Planck Institute for Molecular Biomedicine, Muenster, Germany

Competing interests
The authors declare that no competing interests exist.
Serene C Chng

Institute of Medical Biology, Human Genetics and Embryology Laboratory, A*STAR, Singapore, Singapore

Competing interests
The authors declare that no competing interests exist.
Friedemann Kiefer

n/a, Max Planck Institute for Molecular Biomedicine, Muenster, Germany

Competing interests
The authors declare that no competing interests exist.
Bruno Reversade

Institute of Medical Biology, Human Genetics and Embryology Laboratory, A*STAR, Sinagapore, Singapore

Competing interests
The authors declare that no competing interests exist.
Wiebke Herzog

n/a, University of Muenster, Muenster, Germany

For correspondence
wiebke.herzog@mpi-muenster.mpg.de

Competing interests
The authors declare that no competing interests exist.

Ethics

Animal experimentation: All animal experiments were performed in strict accordance with the relevant laws and institutional guidelines the Max Planck Institute for Molecular Biomedicine, Muenster and the Institute of Medical Biology, Singapore. All protocols were approved by animal ethics committees of the state of North Rhine-Westfalia (Germany,# 39.32.7.1) and Singapore, respectively, and all efforts were made to minimize suffering.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.