J Clin Invest 2014 Jul 1;124(7):3230-40. doi: 10.1172/JCI75181.
Brunet, I; Gordon, E; Han, J; Cristofaro, B; Broqueres-You, D; Liu, C; Bouvrée, K; Zhang, J; Toro, R Del; Mathivet, T; Larrivée, B; Jagu, J; Pibouin-Fragner, L; Pardanaud, L; Machado, MJ; Kennedy, TE; Zhuang, Z; Simons, M; Levy, BI; Tessier-Lavigne, M; Grenz, A; Eltzschig, H; Eichmann, A
Centre Interdisciplinaire de Recherche en Biologie (CIRB), Collège de France, Inserm U1050/CNRS UMR7241, Paris, France. Paris Cardiovascular Research Center (PARCC), INSERM U970, Paris, France. Yale Cardiovascular Research Center, Yale University School
Abstract:
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.
The team at Ozgene has over two decades of experience creating customised knockout and knock-in mice for pivotal medical research globally. Over 400 scientific publications are based on research using Ozgene mice.