Journal Article

Netrin-1 controls sympathetic arterial innervation

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

2014

Overview

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.

• Publisher: American Society for Clinical Investigation
• Subject: Animals / Animals, Newborn / Biological control systems / Biomedical research / Body temperature / DCC Receptor / Female / Gene expression / Genetic aspects / Growth Cones - physiology / Hypertension / Laboratory animals / Lasers / Male / Mesenteric Arteries - growth & development / Mesenteric Arteries - innervation / Mesenteric Arteries - physiology / Mice / Mice, Knockout / Mice, Mutant Strains / Mice, Transgenic / Microscopy / Models, Neurological / Monitoring systems / Myocytes, Smooth Muscle - physiology / Nerve Growth Factors - deficiency / Nerve Growth Factors - genetics / Nerve Growth Factors - physiology / Nerve proteins / Nervous system / Netrin-1 / Neurogenesis / Physiological research / Pregnancy / Properties / Receptors, Cell Surface - physiology / Rodents / Skin / Smooth muscle / Statistical analysis / Sympathetic Nervous System - growth & development / Sympathetic Nervous System - physiology / Tumor Suppressor Proteins - deficiency / Tumor Suppressor Proteins - genetics / Tumor Suppressor Proteins - physiology / Vasoconstriction - physiology / Veins & arteries