title: Emergent growth cone responses to combinations of Slit1 and Netrin 1 in thalamocortical axon topography.
abstract: How guidance cues are integrated during the formation of complex axonal tracts remains largely unknown. Thalamocortical axons (TCAs), which convey sensory and motor information to the neocortex, have a rostrocaudal topographic organization initially established within the ventral telencephalon [1-3]. Here, we show that this topography is set in a small hub, the corridor, which contains matching rostrocaudal gradients of Slit1 and Netrin 1. Using in vitro and in vivo experiments, we show that Slit1 is a rostral repellent that positions intermediate axons. For rostral axons, although Slit1 is also repulsive and Netrin 1 has no chemotactic activity, the two factors combined generate attraction. These results show that Slit1 has a dual context-dependent role in TCA pathfinding and furthermore reveal that a combination of cues produces an emergent activity that neither of them has alone. Our study thus provides a novel framework to explain how a limited set of guidance cues can generate a vast diversity of axonal responses necessary for proper wiring of the nervous system.
authors: INSERM, U1024, Avenir Team, 75005 Paris, France.
authors: Franck
authors: F
authors: Bielle
authors: Paula
authors: P
authors: Marcos-Mondéjar
authors: Eduardo
authors: E
authors: Leyva-Díaz
authors: Ludmilla
authors: L
authors: Lokmane
authors: Erik
authors: E
authors: Mire
authors: Caroline
authors: C
authors: Mailhes
authors: Maryama
authors: M
authors: Keita
authors: Noelia
authors: N
authors: García
authors: Marc
authors: M
authors: Tessier-Lavigne
authors: Sonia
authors: S
authors: Garel
authors: Guillermina
authors: G
authors: López-Bendito
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D019556:COS Cells; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism; D002522:Chlorocebus aethiops; D036386:Ephrin-A5 / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020439:Growth Cones / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000075388:Netrin-1; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism; D013788:Thalamus / Q000196:embryology* / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism; D000097905:Roundabout Proteins
chemical_list: D036386:Ephrin-A5; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000075388:Netrin-1; D011971:Receptors, Immunologic; D040121:Semaphorin-3A; D025521:Tumor Suppressor Proteins; D001616:beta-Galactosidase; D000097905:Roundabout Proteins; C000617353:Ntn1 protein, mouse; C498888:Robo2 protein, mouse; C488217:Sema3a protein, mouse; C120010:Slit1 protein, mouse