title: Cux1 Enables Interhemispheric Connections of Layer II/III Neurons by Regulating Kv1-Dependent Firing.
abstract: 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.
authors.affiliation: Centro Nacional de Biotecnología (CNB-CSIC), Campus de Cantoblanco, Darwin 3, 28049 Madrid, Spain.
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: Rodríguez-Tornos
authors.affiliation: Centro Nacional de Biotecnología (CNB-CSIC), Campus de Cantoblanco, Darwin 3, 28049 Madrid, Spain.
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Briz
authors.affiliation: Centro Nacional de Biotecnología (CNB-CSIC), Campus de Cantoblanco, Darwin 3, 28049 Madrid, Spain.
authors.forename: Linnea A
authors.initials: LA
authors.lastname: Weiss
authors.affiliation: Centro Nacional de Biotecnología (CNB-CSIC), Campus de Cantoblanco, Darwin 3, 28049 Madrid, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Sebastián-Serrano
authors.affiliation: Centro Nacional de Biotecnología (CNB-CSIC), Campus de Cantoblanco, Darwin 3, 28049 Madrid, Spain; Departamento de Matemáticas Universidad Carlos III de Madrid, Grupo Interdisciplinar de Sistemas Complejos (GISC), 28911 Leganés, Madrid, Spain.
authors.forename: Saúl
authors.initials: S
authors.lastname: Ares
authors.affiliation: Centro de Biología Molecular "Severo Ochoa," Consejo Superior de Investigaciones Científicas (CSIC-UAM), 28049 Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Navarrete
authors.affiliation: Department of Basic Neurosciences, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Frangeul
authors.affiliation: HSCRB Harvard University, Cambridge, MA 02138, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Galazo
authors.affiliation: Department of Basic Neurosciences, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Denis
authors.initials: D
authors.lastname: Jabaudon
authors.affiliation: Centro de Biología Molecular "Severo Ochoa," Consejo Superior de Investigaciones Científicas (CSIC-UAM), 28049 Madrid, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Esteban
authors.affiliation: Centro Nacional de Biotecnología (CNB-CSIC), Campus de Cantoblanco, Darwin 3, 28049 Madrid, Spain. Electronic address: mnlopez@cnb.csic.es.
authors.forename: Marta
authors.initials: M
authors.lastname: Nieto
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D003337:Corpus Callosum / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism*; D061251:Primary Cell Culture; D012097:Repressor Proteins / Q000378:metabolism*; D051637:Shaker Superfamily of Potassium Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: C000624101:Cux1 protein, mouse; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D051637:Shaker Superfamily of Potassium Channels