Nerve‐Vessel Interactions During Vertebrate Development

During vertebrate development, the nervous and vascular systems develop similar anatomical architecture and branching pattern but functionally distinct. We are interested in cellular and molecular mechanisms by which these two systems coordinate their development. We have found that in the embryonic skin, peripheral nerves control the patterns of blood vessel branching and arterial differentiation. As a result, the arteries run along the nerves. The facts that nerves secrete vascular endothelial growth factor‐A (VEGF)‐A which stimulates arterial differentiation in vitro, and neuropilin‐1 (NRP1), a co‐receptor for VEGF‐A, is preferentially expressed by artery, suggest that nerve‐derived VEGF‐A may function to induce arteries via NRP1. Using a nerve‐specific deletion of Vegf‐A and endothelial cell specific deletion of Nrp1 in mice , we have shown that nerve‐VEGF‐A signal is required for the nerve‐dependent arterial differentiation in vivo. Surprisingly, nerve‐vessel alignment occurs normally in these conditional mutants, despite the defect in arterial differentiation. This genetic dissociation of arterial differentiation from nerve‐vessel alignment, by inhibition of the VEGF signals, suggests that the alignment and patterning process may require nerve‐derived signals distinct from VEGF.