The role of endoderm in vascular patterning

Angioblasts, the precursor cells that give rise to the endothelial layer of blood vessels, arise from a purely mesodermal population. Individual angioblasts coalesce to form the primary vascular plexus through a process called vasculogenesis. A number of reports in the literature suggest that signals from the adjacent endoderm are necessary to induce angioblast specification within the mesoderm. We present evidence, using both embryological and molecular techniques, indicating that endoderm is not necessary for the induction of angioblasts. While Xenopus embryos lacking endoderm contain aggregates of angioblasts, these angioblasts fail to assemble into endothelial tubes. Endothelial tube formation can be rescued however, by implantation of endodermal tissue from sibling embryos. Based on these studies in Xenopus, and corroborating experiments using the quail embryo, we conclude that endoderm is not required for angioblast specification, but does provide an inductive signal for vascular assembly. In additional experiments using avian embryos, we demonstrate the molecular identity of this inductive signal, showing that endodermally derived Sonic Hedgehog is both necessary and sufficient to form endothelial tubes from angioblasts in avian embryos. This demonstrates a novel role for hedgehog signaling in vascular development and provides a molecular model for vascular assembly.