期刊
CURRENT BIOLOGY
卷 21, 期 20, 页码 1748-1755出版社
CELL PRESS
DOI: 10.1016/j.cub.2011.09.008
关键词
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资金
- INSERM
- City of Paris
- European Young Investigator (EURYI) program
- Spanish Ministry of Science and Innovation [BFU2006-00408/BFI, BFU2009-08261]
- Human Frontier Science Program research grant [RGP29/2008]
- CONSOLIDER [CSD2007-00023]
- Program of Integrated Actions (PAI) Picasso
- French Ministry of Research
- Association pour la Recherche sure Cancer
- CSIC
- EURYI awardee
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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