title: Netrin-1 controls sympathetic arterial innervation.
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.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Brunet
authors.forename: Emma
authors.initials: E
authors.lastname: Gordon
authors.forename: Jinah
authors.initials: J
authors.lastname: Han
authors.forename: Brunella
authors.initials: B
authors.lastname: Cristofaro
authors.forename: Dong
authors.initials: D
authors.lastname: Broqueres-You
authors.forename: Chun
authors.initials: C
authors.lastname: Liu
authors.forename: Karine
authors.initials: K
authors.lastname: Bouvrée
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Zhang
authors.forename: Raquel
authors.initials: R
authors.lastname: del Toro
authors.forename: Thomas
authors.initials: T
authors.lastname: Mathivet
authors.forename: Bruno
authors.initials: B
authors.lastname: Larrivée
authors.forename: Julia
authors.initials: J
authors.lastname: Jagu
authors.forename: Laurence
authors.initials: L
authors.lastname: Pibouin-Fragner
authors.forename: Luc
authors.initials: L
authors.lastname: Pardanaud
authors.forename: Maria J C
authors.initials: MJ
authors.lastname: Machado
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Kennedy
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhuang
authors.forename: Michael
authors.initials: M
authors.lastname: Simons
authors.forename: Bernard I
authors.initials: BI
authors.lastname: Levy
authors.forename: Marc
authors.initials: M
authors.lastname: Tessier-Lavigne
authors.forename: Almut
authors.initials: A
authors.lastname: Grenz
authors.forename: Holger
authors.initials: H
authors.lastname: Eltzschig
authors.forename: Anne
authors.initials: A
authors.lastname: Eichmann
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000075389:DCC Receptor; D005260:Female; D020439:Growth Cones / Q000502:physiology; D008297:Male; D008638:Mesenteric Arteries / Q000254:growth & development / Q000294:innervation* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008959:Models, Neurological; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D009414:Nerve Growth Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000075388:Netrin-1; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000502:physiology; D013564:Sympathetic Nervous System / Q000254:growth & development / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D000075389:DCC Receptor; C501910:Dcc protein, mouse; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1