Emergent Growth Cone Responses to Combinations of Slit1 and Netrin 1 in Thalamocortical Axon Topography

• Published in: Current biology 2011-10, Vol.21 (20), p.1748-1755
• Main Authors: Bielle, Franck, Marcos-Mondéjar, Paula, Leyva-Díaz, Eduardo, Lokmane, Ludmilla, Mire, Erik, Mailhes, Caroline, Keita, Maryama, García, Noelia, Tessier-Lavigne, Marc, Garel, Sonia, López-Bendito, Guillermina
• Format: Article
• Language: English
• Subjects: Animals; Axon guidance; axons; Axons - physiology; beta-Galactosidase - genetics; beta-Galactosidase - metabolism; Cerebral Cortex - embryology; Cerebral Cortex - metabolism; chemotaxis; Chlorocebus aethiops; Cortex; COS Cells; Ephrin-A5 - genetics; Ephrin-A5 - metabolism; Gene Expression Regulation, Developmental; Growth cones; Growth Cones - physiology; in vivo studies; Life Sciences; Mice; Mice, Transgenic; neocortex; Nerve Growth Factors - genetics; Nerve Growth Factors - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nervous system; Netrin-1; Neurobiology; Neurons and Cognition; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Repellents; Roundabout Proteins; Semaphorin-3A - genetics; Semaphorin-3A - metabolism; Telencephalon; Thalamus; Thalamus - embryology; Thalamus - physiology; Topography; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2011.09.008

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. ► The corridor is a decision point for the subpallial topography of TCAs ► Slit1 acts as a rostral repellent to position intermediate TCAs ► The repellent Slit1 enables Netrin 1 attractive activity on rostral axons ► The combination of two cues can elicit a response that neither of them has alone