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
Isabelle Brunet, Emma Gordon, Jinah Han, Brunella Cristofaro, Dong Broqueres-You, Chun Liu, Karine Bouvrée, Jiasheng Zhang, Raquel del Toro, Thomas Mathivet, Bruno Larrivée, Julia Jagu, Laurence Pibouin-Fragner, Luc Pardanaud, Maria J.C. Machado, Timothy E. Kennedy, Zhen Zhuang, Michael Simons, Bernard I. Levy, Marc Tessier-Lavigne, Almut Grenz, Holger Eltzschig, Anne Eichmann
Sympathetic arterial innervation in mice occurs after birth.