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.
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,# 220.127.116.11) and Singapore, respectively, and all efforts were made to minimize suffering.
- Tanya T Whitfield, University of Sheffield, United Kingdom
© 2015, Helker et al.
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