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.
Highlights
In the vertebrate embryo, the formation of the large axial vessels, namely the dorsal aorta (DA) and the cardinal vein (CV), establishes a first circulatory loop and thereby the core of the developing cardiovascular system
Angioblasts are initially specified in the lateral plate mesoderm and migrate between the somites towards the midline, where they coalesce and assemble the DA and the CV underneath the notochord (NC) (Figure 1A,B–F, Video 1)
It has been previously proposed that this process is regulated by Vascular endothelial growth factor A (VEGF-A) (Coultas et al, 2005; Verma et al, 2010; Gore et al, 2012), a master regulator of vascular growth in the embryonic and adult organism
Summary
The formation of the large axial vessels, namely the dorsal aorta (DA) and the cardinal vein (CV), establishes a first circulatory loop and thereby the core of the developing cardiovascular system. As previously published (Nicoli et al, 2008), expression analysis of vegfaa, the gene for the main VEGF-A ortholog in zebrafish, showed the presence of transcripts in the somites between 12 and 15 hr post fertilization (hpf), that is the stage when angioblasts migrate to the midline (see Figure 1B–F).
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