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

2011; Elsevier BV; Volume: 21; Issue: 20 Linguagem: Inglês

10.1016/j.cub.2011.09.008

1879-0445

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

Developmental Biology and Gene Regulation

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 [1López-Bendito G. Molnár Z. Thalamocortical development: how are we going to get there?.Nat. Rev. Neurosci. 2003; 4: 276-289Crossref PubMed Scopus (349) Google Scholar, 2Garel S. Rubenstein J.L.R. Intermediate targets in formation of topographic projections: inputs from the thalamocortical system.Trends Neurosci. 2004; 27: 533-539Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar, 3Vanderhaeghen P. Polleux F. Developmental mechanisms patterning thalamocortical projections: intrinsic, extrinsic and in between.Trends Neurosci. 2004; 27: 384-391Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar]. 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.