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

Bielle, F., Marcos-Mondejar, P., Leyva-Diaz, E., Lokmane, L., Mire, E. ORCID:, Mailhes, C., Keita, M., Garcia, N., Tessier-Lavigne, M., Garel, S. and Lopez-Bendito, G. 2011. Emergent growth cone responses to combinations of Slit1 and Netrin 1 in thalamocortical axon topography. Current Biology 21 (20) , pp. 1748-1755. 10.1016/j.cub.2011.09.008

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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, 2, 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Elsevier (Cell Press)
ISSN: 0960-9822
Date of Acceptance: 1 September 2011
Last Modified: 25 Oct 2022 13:13

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