title: The Specification of Cortical Subcerebral Projection Neurons Depends on the Direct Repression of TBR1 by CTIP1/BCL11a.
abstract: The acquisition of distinct neuronal fates is fundamental for the function of the cerebral cortex. We find that the development of subcerebral projections from layer 5 neurons in the mouse neocortex depends on the high levels of expression of the transcription factor CTIP1; CTIP1 is coexpressed with CTIP2 in neurons that project to subcerebral targets and with SATB2 in those that project to the contralateral cortex. CTIP1 directly represses Tbr1 in layer 5, which appears as a critical step for the acquisition of the subcerebral fate. In contrast, lower levels of CTIP1 in layer 6 are required for TBR1 expression, which directs the corticothalamic fate. CTIP1 does not appear to play a critical role in the acquisition of the callosal projection fate in layer 5. These findings unravel a key step in the acquisition of cell fate for closely related corticofugal neurons and indicate that differential dosages of transcriptions factors are critical to specify different neuronal identities.
authors.affiliation: Biomedical Neuroscience Institute and Program of Physiology and Biophysics, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile.
authors.forename: José
authors.identifier: http://orcid.org/0000-0002-5568-9576
authors.initials: J
authors.lastname: Cánovas
authors.affiliation: Biomedical Neuroscience Institute and Program of Physiology and Biophysics, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile.
authors.forename: F Andrés
authors.initials: FA
authors.lastname: Berndt
authors.affiliation: Center for Biomedical Research and FONDAP Center for Genome Regulation, Universidad Andrés Bello, Santiago 8370146, Chile, and.
authors.forename: Hugo
authors.initials: H
authors.lastname: Sepúlveda
authors.affiliation: Center for Biomedical Research and FONDAP Center for Genome Regulation, Universidad Andrés Bello, Santiago 8370146, Chile, and.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Aguilar
authors.affiliation: Center for Biomedical Research and FONDAP Center for Genome Regulation, Universidad Andrés Bello, Santiago 8370146, Chile, and.
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Veloso
authors.affiliation: Center for Biomedical Research and FONDAP Center for Genome Regulation, Universidad Andrés Bello, Santiago 8370146, Chile, and.
authors.forename: Martín
authors.initials: M
authors.lastname: Montecino
authors.affiliation: Biomedical Neuroscience Institute and Program of Physiology and Biophysics, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Oliva
authors.affiliation: Biomedical Neuroscience Institute and Program of Physiology and Biophysics, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile, Department of Otolaryngology, Hospital Clínico, Universidad de Chile, Santiago 8380456, Chile.
authors.forename: Juan C
authors.identifier: http://orcid.org/0000-0002-1586-4608
authors.initials: JC
authors.lastname: Maass
authors.affiliation: Biomedical Neuroscience Institute and Program of Physiology and Biophysics, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile, kukuljan@med.uchile.cl jimena@neuro.med.uchile.cl.
authors.forename: Jimena
authors.initials: J
authors.lastname: Sierralta
authors.affiliation: Biomedical Neuroscience Institute and Program of Physiology and Biophysics, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile, kukuljan@med.uchile.cl jimena@neuro.med.uchile.cl.
authors.forename: Manuel
authors.initials: M
authors.lastname: Kukuljan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000089622:Doublecortin Domain Proteins; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009434:Neural Pathways / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins; D020825:T-Box Domain Proteins / Q000378:metabolism
chemical_list: C407733:Bcl11a protein, mouse; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D000089622:Doublecortin Domain Proteins; C491198:Eomes protein, mouse; D006657:Histones; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; C492271:Tbr1 protein, mouse
keywords: CTIP1; CTIP2; TBR1; cerebral cortex; in utero electroporation; subcerebral projection neurons