title: Netrin-1 is required for commissural axon guidance in the developing vertebrate nervous system.
abstract: During nervous system development, spinal commissural axons project toward floor plate cells and trochlear motor axons extend away from these cells. Netrin-1, a diffusible protein made by floor plate cells, can attract spinal commissural axons and repel trochlear axons in vitro, but its role in vivo is unknown. Netrin-1 deficient mice exhibit defects in spinal commissural axon projections that are consistent with netrin-1 guiding these axons. Defects in several forebrain commissures are also observed, suggesting additional guidance roles for netrin-1. Trochlear axon projections are largely normal, predicting the existence of additional cues for these axons, and evidence is provided for a distinct trochlear axon chemorepellent produced by floor plate cells. These results establish netrin-1 as a guidance cue that likely collaborates with other diffusible cues to guide axons in vivo.
authors.affiliation: Howard Hughes Medical Institute, Department of Anatomy, University of California, San Francisco 94143-0452, USA.
authors.forename: T
authors.initials: T
authors.lastname: Serafini
authors.forename: S A
authors.initials: SA
authors.lastname: Colamarino
authors.forename: E D
authors.initials: ED
authors.lastname: Leonardo
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Beddington
authors.forename: W C
authors.initials: WC
authors.lastname: Skarnes
authors.forename: M
authors.initials: M
authors.lastname: Tessier-Lavigne
mesh_terms: D000483:Alleles; D000818:Animals; D001369:Axons / Q000502:physiology*; D015139:Blotting, Southern; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006720:Homozygote; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D009046:Motor Neurons / Q000502:physiology / Q000648:ultrastructure; D009154:Mutation / Q000502:physiology; D009414:Nerve Growth Factors / Q000032:analysis / Q000235:genetics*; D000075388:Netrin-1; D011149:Pons / Q000737:chemistry / Q000166:cytology / Q000196:embryology*; D013116:Spinal Cord / Q000737:chemistry / Q000166:cytology / Q000196:embryology*; D014321:Trochlear Nerve / Q000166:cytology / Q000196:embryology; D025521:Tumor Suppressor Proteins; D014714:Vertebrates
chemical_list: D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1