Abstract
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.
Copyright © 2013 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Age Factors
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Animals
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Axons / physiology
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Body Patterning / genetics
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Calbindin 2
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Cerebral Cortex / cytology
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Cerebral Cortex / physiology*
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Contactin 2 / metabolism
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Cytoskeletal Proteins
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DNA-Binding Proteins / metabolism
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Embryo, Mammalian
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Gene Expression Regulation, Developmental / genetics
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Glycoproteins / genetics
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Homeodomain Proteins / genetics
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Intracellular Signaling Peptides and Proteins
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Leukocyte L1 Antigen Complex / metabolism
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Membrane Glycoproteins / genetics
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Membrane Proteins / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neural Pathways / physiology*
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Nuclear Proteins / metabolism
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POU Domain Factors / genetics
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Repressor Proteins / metabolism
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S100 Calcium Binding Protein G / metabolism
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Semaphorins
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T-Box Domain Proteins
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Thalamus / cytology
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Thalamus / physiology*
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Thyroid Nuclear Factor 1
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Tumor Suppressor Proteins / metabolism
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Wnt3A Protein / genetics
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tau Proteins / genetics
Substances
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Bcl11b protein, mouse
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Calbindin 2
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Cntn2 protein, mouse
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Contactin 2
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Glycoproteins
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Homeodomain Proteins
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Intracellular Signaling Peptides and Proteins
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Leukocyte L1 Antigen Complex
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Luminescent Proteins
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Membrane Glycoproteins
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Membrane Proteins
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Nerve Tissue Proteins
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Nuclear Proteins
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POU Domain Factors
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Plxnd1 protein, mouse
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Repressor Proteins
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S100 Calcium Binding Protein G
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Sema3e protein, mouse
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Semaphorins
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T-Box Domain Proteins
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Tbr1 protein, mouse
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Thyroid Nuclear Factor 1
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Transcription Factors
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Tumor Suppressor Proteins
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Wnt3A Protein
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Zfpm2 protein, mouse
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empty spiracles homeobox proteins
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tau Proteins
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Pou3f4 protein, mouse