Journal
NEURON
Volume 77, Issue 3, Pages 472-484Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2012.11.031
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Funding
- NIH [37 MH059962]
- NINDS [065048]
- Fond National Suisse (FNS) [31003A_122550]
- CNRS
- Aix-Marseille Universite
- Federation pour la Recherche sur le Cerveau
- Institut Universitaire de France
- INSERM Avenir Program
- City of Paris Start-up Program
- EURYI program
- French Ministry of Research and Fondation ARC pour la recherche sur le cancer
- Fondation ARC pour la recherche sur le cancer
- EMBO YIP
- Swiss National Science Foundation (SNF) [31003A_122550] Funding Source: Swiss National Science Foundation (SNF)
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Major outputs of the neocortex are conveyed by corticothalamic axons (CTAs), which form reciprocal connections with thalamocortical axons, and corticosubcerebral axons (CSAs) headed to more caudal parts of the nervous system. Previous findings establish that transcriptional programs define cortical neuron identity and suggest that CTAs and thalamic axons may guide each other, but the mechanisms governing CTA versus CSA pathfinding remain elusive. Here, we show that thalamocortical axons are required to guide pioneer CTAs away from a default CSA-like trajectory. This process relies on a hold in the progression of cortical axons, or waiting period, during which thalamic projections navigate toward cortical axons. At the molecular level, Sema3E/PlexinD1 signaling in pioneer cortical neurons mediates a waiting signal required to orchestrate the mandatory meeting with reciprocal thalamic axons. Our study reveals that temporal control of axonal progression contributes to spatial pathfinding of cortical projections and opens perspectives on brain wiring.
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