Abstract:
: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.
journal_name
Proc Natl Acad Sci U S Aauthors
Park KW,Crouse D,Lee M,Karnik SK,Sorensen LK,Murphy KJ,Kuo CJ,Li DYdoi
10.1073/pnas.0405984101keywords:
subject
Has Abstractpub_date
2004-11-16 00:00:00pages
16210-5issue
46eissn
0027-8424issn
1091-6490pii
0405984101journal_volume
101pub_type
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