Emergent Growth Cone Responses to Combinations of Slit1 and Netrin 1 in Thalamocortical Axon Topography
2011
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
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.
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