Cux1 Enables Interhemispheric Connections of Layer II/III Neurons by Regulating Kv1-Dependent Firing
| Autor: | Laura Frangeul, José A. Esteban, Maria J. Galazo, Carlos G. Briz, Linnea A. Weiss, Álvaro Sebastián-Serrano, Saúl Ares, Denis Jabaudon, Marta Nieto, Marta Navarrete, Fernanda M. Rodríguez-Tornos |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Action Potentials/physiology Shaker Superfamily of Potassium Channels/biosynthesis/genetics/physiology Neuroscience(all) Transgene Primary Cell Culture Axonal loss Action Potentials Mice Transgenic Biology Corpus callosum Corpus Callosum Mice 03 medical and health sciences 0302 clinical medicine medicine Transcriptional regulation Animals Homeodomain Proteins/metabolism Corpus Callosum/cytology/growth & development/physiology Transcription factor Nuclear Proteins/metabolism Homeodomain Proteins Neurons Regulation of gene expression Neocortex Repressor Proteins/metabolism General Neuroscience Nuclear Proteins Gene Expression Regulation Developmental Potassium channel ddc:616.8 Repressor Proteins 030104 developmental biology medicine.anatomical_structure nervous system Gene Knockdown Techniques Shaker Superfamily of Potassium Channels Neurons/physiology Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Neuron, Vol. 89, No 3 (2016) pp. 494-506 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2015.12.020 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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