期刊
NEURON
卷 89, 期 3, 页码 494-506出版社
CELL PRESS
DOI: 10.1016/j.neuron.2015.12.020
关键词
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资金
- La Caixa Foundation
- Spanish Ministerio de Ciencia e Innovacion (MICINN) [FPI-BES-2012-056011, JCI-2012-14147]
- J.A.E.-Doc contract from the CSIC program Junta para la Ampliacion de Estudios'' [JAEDOC014]
- European Social Fund
- grant PHYSDEV [FIS2012-32349]
- BBVA Foundation from MICINN [CSD2010-00045, SAF2011-24730]
- Ramon Areces Foundation
- MICINN [SAF2011-23735, BFU2014-55738-REDT]
Neuronal subtype-specific transcription factors (TFs) instruct key features of neuronal function and connectivity. Activity-dependent mechanisms also contribute to wiring and circuit assembly, but whether and how they relate to TF-directed neuronal differentiation is poorly investigated. Here we demonstrate that the TF Cux1 controls the formation of the layer II/III corpus callosum (CC) projections through the developmental transcriptional regulation of Kv1 voltage-dependent potassium channels and the resulting postnatal switch to a Kv1-dependent firing mode. Loss of Cux1 function led to a decrease in the expression of Kv1 transcripts, aberrant firing responses, and selective loss of CC contralateral innervation. Firing and innervation were rescued by re-expression of Kv1 or postnatal reactivation of Cux1. Knocking down Kv1 mimicked Cux1-mediated CC axonal loss. These findings reveal that activity-dependent processes are central bona fide components of neuronal TF-differentiation programs and establish the importance of intrinsic firing modes in circuit assembly within the neocortex.
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