Properties and fate of oligodendrocyte progenitor cells in the corpus callosum, motor cortex, and piriform cortex of the mouse
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Oligodendrocyte progenitor cells (OPCs) in the postnatal mouse corpus callosum (CC) and motor cortex (Ctx) reportedly generate only oligodendrocytes (OLs), whereas those in the piriform cortex may also generate neurons. OPCs have also been subdivided based on their expression of voltage-gated ion channels, ability to respond to neuronal activity, and proliferative state. To determine whether OPCs in the piriform cortex have inherently different physiological properties from those in the CC and Ctx, we studied acute brain slices from postnatal transgenic mice in which GFP expression identifies OL lineage cells. We whole-cell patch clamped GFP-expressing (GFP(+)) cells within the CC, Ctx, and anterior piriform cortex (aPC) and used prelabeling with 5-ethynyl-2'-deoxyuridine (EdU) to assess cell proliferation. After recording, slices were immunolabeled and OPCs were defined by strong expression of NG2. NG2(+) OPCs in the white and gray matter proliferated and coexpressed PDGFRα and voltage-gated Na(+) channels (I(Na)). Approximately 70% of OPCs were capable of generating regenerative depolarizations. In addition to OLIG2(+) NG2(+) I(Na)(+) OPCs and OLIG2(+) NG2(neg) I(Na)(neg) OLs, we identified cells with low levels of NG2 limited to the soma or the base of some processes. These cells had a significantly reduced I(Na) and a reduced ability to incorporate EdU when compared with OPCs and probably correspond to early differentiating OLs. By combining EdU labeling and lineage tracing using Pdgfrα-CreER(T2) : R26R-YFP transgenic mice, we double labeled OPCs and traced their fate in the postnatal brain. These OPCs generated OLs but did not generate neurons in the aPC or elsewhere at any time that we examined.
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By cumulative labeling with EdU, all OPs throughout the adult CNS can be labeled (GF≈100%), indicating that all OPs are capable of undergoing cell division.
“Now, by cumulative labeling with EdU (which does not require antigen retrieval), we are able to label all OPs throughout the adult CNS (GF≈100%), indicating that all OPs are capable of undergoing cell division (Clarke et al., 2012; this paper).”
From Oligodendrocyte Dynamics in the Healthy Adult CNS: Evidence for Myelin Remodeling (2013) · cites this paper as Clarke et al., 2012
The Results section reports that cumulative EdU labeling marked >98% of OPCs in the anterior piriform cortex of mice labeled from P60 and concludes that these OPCs are mitotically active. The Methods section also states that EdU detection does not require antigen retrieval. The paper does not establish a growth fraction of approximately 100% throughout the entire adult CNS; its observations concern selected mouse brain regions. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe Cre/lox system has been used in reporter mice to track oligodendrogenesis and myelin synthesis during development, after CNS demyelination, and after SCI.
“The Cre/lox system been used in reporter mice to track oligodendrogenesis and myelin synthesis during development [45, 81], after CNS demyelination [82, 83], and after SCI [44, 84, 85].”
From Delayed short-term tamoxifen treatment does not promote remyelination or neuron sparing after spinal cord injury (2020) · cites this paper as [81]
The Methods (Transgenic mice) and Results (OPCs generate exclusively OLs in the postnatal mouse brain; page unavailable) show that the study used Cre-lox reporter mice to trace OPCs into oligodendrocytes in the postnatal brain. This supports the citation’s developmental oligodendrogenesis point, but the cited passages do not show that the reporters tracked myelin synthesis. The demyelination and SCI parts of the sentence have separate citations and are not attributed to this paper. (LLM, conf=0.87)
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“They administrated tamoxifen at P4, P30, P45, and P180 and then analyzed the progeny after days or months to analyze whether NG2 glia produced astrocytes in the postnatal brain (Rivers et al., 2008; Kang et al., 2010; Clarke et al., 2012).”
BackgroundA New Outlook on Mental Illnesses: Glial Involvement Beyond the Glue
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- Authors
- Clarke, L. E., Young, K. M., Hamilton, N. B., Li, H., Richardson, W. D., & Attwell, D.
- Affiliations
- University College London (GB)
- University of Tasmania (AU)
- Corresponding author
- Attwell, D.
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-06-13
- Volume
- 32
- Issue
- 24
- Pages
- 8173-8185
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3378033
- OpenAlex
- W2093202798
- Cited by
- 182
- References
- 65
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 5 · 2023: 12 · 2022: 8 · 2021: 12 · 2020: 15 · 2019: 14 · 2018: 16 · 2017: 15 · 2016: 19 · 2015: 24 · 2014: 16 · 2013: 16 · 2012: 1
- FWCI
- 6.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eCite Digital Repository (University of Tasmania) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Wellcome Trust (080513, 86419, 017948, 075232)
- Alzheimer's Society
- Bupa Foundation
- European Commission
- National Institutes of Health
- Medical Research Council
- National Health and Medical Research Council (1030939)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Keywords
- oligodendrocyte precursor cells, corpus callosum, motor cortex, piriform cortex, NG2, PDGFRA, voltage-gated sodium channels, oligodendrocyte differentiation, neuronal lineage, cell fate, postnatal brain development, Olig2, lineage tracing
- MeSH terms
- Chondroitin Sulfate Proteoglycan 4, Animals, Antigens, Cell Differentiation, Corpus Callosum, Female, Male, Membrane Potentials, Mice, Transgenic, Motor Cortex, Olfactory Pathways, Oligodendroglia, Proteoglycans, Stem Cells, Sodium Channels, Cell Lineage, Receptor, Platelet-Derived Growth Factor alpha, Cell Proliferation, Mice
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