Genome-Wide Target Analyses of Otx2 Homeoprotein in Postnatal Cortex
Open accessAbstract
Juvenile brain has a unique time window, or critical period, in which neuronal circuits are remodeled by experience. Mounting evidence indicates the importance of neuronal circuit rewiring in various neurodevelopmental disorders of human cognition. We previously showed that Otx2 homeoprotein, essential for brain formation, is recaptured during postnatal maturation of parvalbumin-positive interneurons (PV cells) to activate the critical period in mouse visual cortex. Cortical Otx2 is the only interneuron-enriched transcription factor known to regulate the critical period, but its downstream targets remain unknown. Here, we used chromatin immunoprecipitation sequencing (ChIP-seq) to identify genome-wide binding sites of Otx2 in juvenile mouse cortex, and interneuron-specific RNA-seq to explore the Otx2-dependent transcriptome. Otx2-bound genes were associated with human diseases such as schizophrenia as well as critical periods. Of these genes, expression of neuronal factors involved in transcription, signal transduction and mitochondrial function was moderately and broadly affected in Otx2-deficient interneurons. In contrast to reported binding sites in the embryo, genes encoding potassium ion transporters such as KV3.1 had juvenile cortex-specific binding sites, suggesting that Otx2 is involved in regulating fast-spiking properties during PV cell maturation. Moreover, transcripts of oxidative resistance-1 (Oxr1), whose promoter has Otx2 binding sites, were markedly downregulated in Otx2-deficient interneurons. Therefore, an important role of Otx2 may be to protect the cells from the increased oxidative stress in fast-spiking PV cells. Our results suggest that coordinated expression of Otx2 targets promotes PV cell maturation and maintains its function in neuronal plasticity and disease.
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RNA sequencing analysis of PV cells containing Otx2 indicates that Otx2 may be necessary for mitochondrial function, cellular respiration, and redox regulation.
“RNA sequencing analysis of PV cells containing Otx2 indicates that Otx2 may be necessary for mitochondrial function, cellular respiration, and redox regulation (Sakai et al., 2017).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Sakai et al., 2017
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Self-citationThe Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders
Wen, T. H., Binder, D. K., Ethell, I. M., & Razak, K. A. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00270 · Cited by 170 · see citing works
- Authors
- Sakai, A., Nakato, R., Ling, Y., Hou, X., Hara, N., Iijima, T., Yanagawa, Y., Kuwano, R., Okuda, S., Shirahige, K., & Sugiyama, S.
- Affiliations
- Niigata University (JP)
- Institute for Quantitative Biosciences, The University of Tokyo (JP)
- Brain Research Institute, Niigata University (JP)
- Gunma University (JP)
- Corresponding author
- Sugiyama, Sayaka
- ORCID
- Venue
- Frontiers in Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2017-05-31
- Volume
- 11
- Pages
- 307-307
- ISSN
- 1662-453X (ISSN-L)
- PMC
- PMC5450002
- OpenAlex
- W2617330611
- Cited by
- 30
- References
- 75
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 1
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (KAKENHI 22700330, KAKENHI 26430010, KAKENHI 22710183, KAKENHI 2440156, KAKENHI 16K14781, KAKENHI 17H05942)
- Japan Science and Technology Agency (Next Generation World-Leading Researchers LS046, PRESTO program)
- Takeda Science Foundation
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Otx2, parvalbumin interneurons, critical period, Kv3.1 potassium channel, fast spiking, oxidative stress, OXR1, schizophrenia, neuroplasticity, transcriptional regulation
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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