Cell Press, Neuron, 3(77), p. 472-484, 2013
DOI: 10.1016/j.neuron.2012.11.031
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Major outputs of the neocortex are conveyed by corticothalamic axons (CTA), which form reciprocal connections with thalamocortical axons, and corticosubcerebral axons (CSA) headed to more caudal parts of the nervous system. Previous findings establish that transcriptional programs define cortical neurons identity and suggest that CTA 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 CTA 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 towards 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 novel perspectives on brain wiring.