Tbr1 regulates differentiation of the preplate and layer 6
Open accessAbstract
During corticogenesis, early-born neurons of the preplate and layer 6 are important for guiding subsequent neuronal migrations and axonal projections. Tbr1 is a putative transcription factor that is highly expressed in glutamatergic early-born cortical neurons. In Tbr1-deficient mice, these early-born neurons had molecular and functional defects. Cajal-Retzius cells expressed decreased levels of Reelin, resulting in a reeler-like cortical migration disorder. Impaired subplate differentiation was associated with ectopic projection of thalamocortical fibers into the basal telencephalon. Layer 6 defects contributed to errors in the thalamocortical, corticothalamic, and callosal projections. These results show that Tbr1 is a common genetic determinant for the differentiation of early-born glutamatergic neocortical neurons and provide insights into the functions of these neurons as regulators of cortical development.
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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 Hevner et al., 2001
Tbr1−/− mice have defective cortical morphology, neuronal migration, and axonal projections, which are not detected in Tbr1+/− mice.
“Tbr1−/− mice have defective cortical morphology, neuronal migration, and axonal projections [156, 157], which are not detected in Tbr1+/− mice that model the haploinsufficiency observed in patients more faithfully.”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [157]
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- Authors
- Hevner, R. F., Shi, L., Justice, N., Hsueh, Y.-P., Sheng, M., Smiga, S., Bulfone, A., Goffinet, A. M., Campagnoni, A. T., & Rubenstein, J. L. R.
- Affiliations
- University of California, San Francisco (US)
- Howard Hughes Medical Institute (US)
- University of California, Los Angeles (US)
- Corresponding author
- Rubenstein, John L.R
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2001-02
- Volume
- 29
- Issue
- 2
- Pages
- 353-366
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2029245198
- Cited by
- 857
- References
- 53
- Citations by year
- 2026: 20 · 2025: 36 · 2024: 21 · 2023: 29 · 2022: 38 · 2021: 41 · 2020: 41 · 2019: 33 · 2018: 31 · 2017: 36 · 2016: 42 · 2015: 38 · 2014: 40 · 2013: 39 · 2012: 38
- FWCI
- 5.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (submittedVersion)
- Funders
- National Institutes of Health (2k02mh001046-06, 7k08ns001973-06)
- National Institute of Mental Health (K02MH01046)
- National Institute of Neurological Disorders and Stroke (NS01973, R01NS034661)
- 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 › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- Tbr1, cortical development, preplate, layer 6, glutamatergic neurons, Cajal-Retzius cells, reelin, subplate, thalamocortical connections, corticothalamic projections, callosal projections, neuronal migration, transcription factors
- MeSH terms
- Reelin Protein, Animals, Cell Movement, DNA-Binding Proteins, Germ Layers, Lac Operon, Mice, Mutant Strains, Mice, Transgenic, Mutation, Nerve Tissue Proteins, Neural Pathways, Synaptic Transmission, Neurons, Serine Endopeptidases, Cell Adhesion Molecules, Neuronal, Extracellular Matrix Proteins, Cell Death, Gene Expression Regulation, Developmental, Neocortex, T-Box Domain Proteins, Mice
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