SOX5 postmitotically regulates migration, postmigratory differentiation, and projections of subplate and deep-layer neocortical neurons
Open accessAbstract
Neocortical projection neurons exhibit layer-specific molecular profiles and axonal connections. Here we show that the molecular identities of early-born subplate and deep-layer neurons are not acquired solely during generation or shortly thereafter but undergo progressive postmitotic refinement mediated by SOX5. Fezf2 and Bcl11b , transiently expressed in all subtypes of newly postmigratory early-born neurons, are subsequently downregulated in layer 6 and subplate neurons, thereby establishing their layer 5-enriched postnatal patterns. In Sox5 -null mice, this downregulation is disrupted, and layer 6 and subplate neurons maintain an immature differentiation state, abnormally expressing these genes postnatally. Consistent with this disruption, SOX5 binds and represses a conserved enhancer near Fezf2 . The Sox5 -null neocortex exhibits failed preplate partition and laminar inversion of early-born neurons, loss of layer 5 subcerebral axons, and misrouting of subplate and layer 6 corticothalamic axons to the hypothalamus. Thus, SOX5 postmitotically regulates the migration, postmigratory differentiation, and subcortical projections of subplate and deep-layer neurons.
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SOX5 has a known role in mammalian corticogenesis.
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From Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism (2016) · cites this paper as [23]
The observed transcriptome changes are consistent with an ongoing process triggered largely by genetic and prenatal factors but evolving during the first decade of brain development.
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From Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism (2016) · cites this paper as [23]
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- Authors
- Kwan, K. Y., Lam, M. M. S., Krsnik, Ž., Kawasawa, Y. I., Lefebvre, V., & Šestan, N.
- Affiliations
- Yale University (US)
- Department of Cell Biology and Orthopaedic Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-10-14
- Volume
- 105
- Issue
- 41
- Pages
- 16021-16026
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2572944
- OpenAlex
- W1985705162
- Cited by
- 271
- References
- 36
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 15 · 2023: 14 · 2022: 13 · 2021: 18 · 2020: 14 · 2019: 14 · 2018: 10 · 2017: 14 · 2016: 22 · 2015: 19 · 2014: 19 · 2013: 26 · 2012: 14
- FWCI
- 4.49
- 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)
- Funders
- March of Dimes Foundation
- Whitehall Foundation
- Cincinnati Children's Hospital Medical Center
- National Institutes of Health
- Canadian Institutes of Health Research
- RIKEN
- National Institute of Neurological Disorders and Stroke (R01NS054273, NS 054273)
- RIKEN Brain Science Institute
- 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
- SOX5, neuronal migration, subplate neurons, Fezf2, BCL11B, enhancer repression, cortical lamination, neocortex development
- MeSH terms
- Animals, Cell Differentiation, Cell Movement, DNA-Binding Proteins, Mitosis, Neurons, Repressor Proteins, Down-Regulation, Cell Adhesion Molecules, Mice, Knockout, Neocortex, Cell Surface Extensions, Tumor Suppressor Proteins, Mice, SOXD Transcription Factors
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