Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors
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Eye Proteins / genetics
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Eye Proteins / metabolism
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Gene Expression Profiling
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Gene Expression Regulation, Developmental
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Mice
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Mice, Knockout
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Mice, Mutant Strains
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Mice, Transgenic
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Mutation
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Neocortex / embryology*
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Neocortex / metabolism*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Neurons / cytology*
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PAX6 Transcription Factor
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Paired Box Transcription Factors
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Protein Array Analysis
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Receptors, Cytoplasmic and Nuclear / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Eye Proteins
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Homeodomain Proteins
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Nerve Tissue Proteins
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Neurog2 protein, mouse
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Nr2e1 protein, mouse
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PAX6 Transcription Factor
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Paired Box Transcription Factors
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Pax6 protein, mouse
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Receptors, Cytoplasmic and Nuclear
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Repressor Proteins
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Transcription Factors
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Neurog1 protein, mouse