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. 2011 Oct 25;21(20):1748-55.
doi: 10.1016/j.cub.2011.09.008. Epub 2011 Oct 13.

Emergent growth cone responses to combinations of Slit1 and Netrin 1 in thalamocortical axon topography

Franck Bielle  1 , Paula Marcos-Mondéjar, Eduardo Leyva-Díaz, Ludmilla Lokmane, Erik Mire, Caroline Mailhes, Maryama Keita, Noelia García, Marc Tessier-Lavigne, Sonia Garel, Guillermina López-Bendito
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Free article

Emergent growth cone responses to combinations of Slit1 and Netrin 1 in thalamocortical axon topography

Franck Bielle et al. Curr Biol. .
Free article

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.

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