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Publication : Netrin-1 controls sympathetic arterial innervation.

First Author  Brunet I Year  2014
Journal  J Clin Invest Volume  124
Issue  7 Pages  3230-40
PubMed ID  24937433 Mgi Jnum  J:213784
Mgi Id  MGI:5586596 Doi  10.1172/JCI75181
Citation  Brunet I, et al. (2014) Netrin-1 controls sympathetic arterial innervation. J Clin Invest 124(7):3230-40
abstractText  Autonomic sympathetic nerves innervate peripheral resistance arteries, thereby regulating vascular tone and controlling blood supply to organs. Despite the fundamental importance of blood flow control, how sympathetic arterial innervation develops remains largely unknown. Here, we identified the axon guidance cue netrin-1 as an essential factor required for development of arterial innervation in mice. Netrin-1 was produced by arterial smooth muscle cells (SMCs) at the onset of innervation, and arterial innervation required the interaction of netrin-1 with its receptor, deleted in colorectal cancer (DCC), on sympathetic growth cones. Function-blocking approaches, including cell type-specific deletion of the genes encoding Ntn1 in SMCs and Dcc in sympathetic neurons, led to severe and selective reduction of sympathetic innervation and to defective vasoconstriction in resistance arteries. These findings indicate that netrin-1 and DCC are critical for the control of arterial innervation and blood flow regulation in peripheral organs.
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