The axonal attractant Netrin-1 is an angiogenic factor

KW Park, D Crouse, M Lee, SK Karnik… - Proceedings of the …, 2004 - National Acad Sciences
KW Park, D Crouse, M Lee, SK Karnik, LK Sorensen, KJ Murphy, CJ Kuo, DY Li
Proceedings of the National Academy of Sciences, 2004National Acad Sciences
Blood vessels and nerves often follow parallel trajectories, suggesting that distal targets use
common cues that induce vascularization and innervation. Netrins are secreted by the floor
plate and attract commissural axons toward the midline of the neural tube. Here, we show
that Netrin-1 is also a potent vascular mitogen. Netrin-1 stimulates proliferation, induces
migration, and promotes adhesion of endothelial cells and vascular smooth muscle cells
with a specific activity comparable to vascular endothelial growth factor and platelet-derived …
Blood vessels and nerves often follow parallel trajectories, suggesting that distal targets use common cues that induce vascularization and innervation. Netrins are secreted by the floor plate and attract commissural axons toward the midline of the neural tube. Here, we show that Netrin-1 is also a potent vascular mitogen. Netrin-1 stimulates proliferation, induces migration, and promotes adhesion of endothelial cells and vascular smooth muscle cells with a specific activity comparable to vascular endothelial growth factor and platelet-derived growth factor. Our evidence indicates that the netrin receptor, Neogenin, mediates netrin signaling in vascular smooth muscle cells, but suggests that an unidentified receptor mediates the proangiogenic effects of Netrin-1 on endothelial cells. Netrin-1 also stimulates angiogenesis in vivo and augments the response to vascular endothelial growth factor. Thus, we demonstrate that Netrin-1 is a secreted neural guidance cue with the unique ability to attract both blood vessels and axons, and suggest that other cues may also function as vascular endothelial growth factors.
National Acad Sciences