Sequential phases of cortical specification involve Neurogenin-dependent and -independent pathways
Autor: | Carol Schuurmans, Christopher A. Walsh, Hua Tang, Franck Polleux, Lisa-Marie Langevin, Richard H. Dyck, Olivier Britz, Olivier Armant, Craig E. Brown, Jan M Stenman, Kenny Campbell, James M. Cunningham, Julie Seibt, Natalia Klenin, Marta Nieto, François Guillemot |
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Rok vydání: | 2004 |
Předmět: |
PAX6 Transcription Factor
Protein Array Analysis Receptors Cytoplasmic and Nuclear Mice Transgenic Neocortex Nerve Tissue Proteins Biology Neurotransmission Neurogenins Bioinformatics Article General Biochemistry Genetics and Molecular Biology Mice Glutamatergic chemistry.chemical_compound Basic Helix-Loop-Helix Transcription Factors medicine Animals Paired Box Transcription Factors Eye Proteins Neurotransmitter Molecular Biology Homeodomain Proteins Mice Knockout Neurons General Immunology and Microbiology Gene Expression Profiling General Neuroscience Gene Expression Regulation Developmental Mice Mutant Strains Repressor Proteins Corticogenesis medicine.anatomical_structure nervous system chemistry Mutation GABAergic PAX6 Neuroscience Transcription Factors |
Zdroj: | The EMBO Journal. 23:2892-2902 |
ISSN: | 1460-2075 0261-4189 |
DOI: | 10.1038/sj.emboj.7600278 |
Popis: | Neocortical projection neurons, which segregate into six cortical layers according to their birthdate, have diverse morphologies, axonal projections and molecular profiles, yet they share a common cortical regional identity and glutamatergic neurotransmission phenotype. Here we demonstrate that distinct genetic programs operate at different stages of corticogenesis to specify the properties shared by all neocortical neurons. Ngn1 and Ngn2 are required to specify the cortical (regional), glutamatergic (neurotransmitter) and laminar (temporal) characters of early-born (lower-layer) neurons, while simultaneously repressing an alternative subcortical, GABAergic neuronal phenotype. Subsequently, later-born (upper-layer) cortical neurons are specified in an Ngn-independent manner, requiring instead the synergistic activities of Pax6 and Tlx, which also control a binary choice between cortical/glutamatergic and subcortical/GABAergic fates. Our study thus reveals an unanticipated heterogeneity in the genetic mechanisms specifying the identity of neocortical projection neurons. |
Databáze: | OpenAIRE |
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