Tbr1 regulates regional and laminar identity of postmitotic neurons in developing neocortex
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Areas and layers of the cerebral cortex are specified by genetic programs that are initiated in progenitor cells and then, implemented in postmitotic neurons. Here, we report that Tbr1, a transcription factor expressed in postmitotic projection neurons, exerts positive and negative control over both regional (areal) and laminar identity. Tbr1 null mice exhibited profound defects of frontal cortex and layer 6 differentiation, as indicated by down-regulation of gene-expression markers such as Bcl6 and Cdh9 . Conversely, genes that implement caudal cortex and layer 5 identity, such as Bhlhb5 and Fezf2 , were up-regulated in Tbr1 mutants. Tbr1 implements frontal identity in part by direct promoter binding and activation of Auts2 , a frontal cortex gene implicated in autism. Tbr1 regulates laminar identity in part by downstream activation or maintenance of Sox5 , an important transcription factor controlling neuronal migration and corticofugal axon projections. Similar to Sox5 mutants, Tbr1 mutants exhibit ectopic axon projections to the hypothalamus and cerebral peduncle. Together, our findings show that Tbr1 coordinately regulates regional and laminar identity of postmitotic cortical neurons.
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TBR1 encodes a transcription factor that binds DNA and regulates gene expression in the developing brain.
“For example, TBR1 encodes a transcription factor that binds DNA and regulates gene expression in the developing brain (Bedogni et al., 2010; Hevner et al., 2001).”
From Getting to the cores of autism (2019) · cites this paper as Bedogni et al., 2010
Tbr1 regulates expression of rostrocaudal and layer-specific markers in the cerebral cortex, with the rostrocaudal effect partly through activation of AUTS2.
“Tbr1 in turn regulates the expression of rostrocaudal and layer-specific markers in the cerebral cortex, the former being partly through activation of the autism gene AUTS2 [28].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [28]
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“For example, TBR1 encodes a transcription factor that binds DNA and regulates gene expression in the developing brain (Bedogni et al., 2010; Hevner et al., 2001).”
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- Authors
- Bedogni, F., Hodge, R. D., Elsen, G. E., Nelson, B. R., Daza, R. A. M., Beyer, R. P., Bammler, T. K., Rubenstein, J. L. R., & Hevner, R. F.
- Affiliations
- University of Washington (US)
- Seattle Children's Research Institute (US)
- University of California, San Francisco (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-07-06
- Volume
- 107
- Issue
- 29
- Pages
- 13129-13134
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2919950
- OpenAlex
- W2089397711
- Cited by
- 322
- References
- 50
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 12 · 2023: 19 · 2022: 21 · 2021: 26 · 2020: 14 · 2019: 22 · 2018: 16 · 2017: 21 · 2016: 22 · 2015: 29 · 2014: 18 · 2013: 33 · 2012: 27
- FWCI
- 7.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS050248, R01NS034661, R01NS099099)
- National Institute of Environmental Health Sciences (P30 ES-07033, P30ES007033)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD02274, P30HD002274)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Tbr1, neocortex development, frontal cortex, layer 6, layer 5, AUTS2, SOX5, neuronal migration, Fezf2, BCL6, transcriptional regulation, autism spectrum disorder
- MeSH terms
- Animals, Cytoskeletal Proteins, DNA-Binding Proteins, Mitosis, Mutation, Neurons, Nuclear Proteins, Organ Specificity, Protein Binding, Transcription Factors, Biomarkers, Transcriptional Activation, Down-Regulation, Up-Regulation, Gene Expression Regulation, Developmental, Neocortex, Oligonucleotide Array Sequence Analysis, T-Box Domain Proteins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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