Phosphorylation State of Olig2 Regulates Proliferation of Neural Progenitors
Open accessAbstract
The bHLH transcription factors that regulate early development of the central nervous system can generally be classified as either antineural or proneural. Initial expression of antineural factors prevents cell cycle exit and thereby expands the pool of neural progenitors. Subsequent (and typically transient) expression of proneural factors promotes cell cycle exit, subtype specification, and differentiation. Against this backdrop, the bHLH transcription factor Olig2 in the oligodendrocyte lineage is unorthodox, showing antineural functions in multipotent CNS progenitor cells but also sustained expression and proneural functions in the formation of oligodendrocytes. We show here that the proliferative function of Olig2 is controlled by developmentally regulated phosphorylation of a conserved triple serine motif within the amino-terminal domain. In the phosphorylated state, Olig2 maintains antineural (i.e., promitotic) functions that are reflected in human glioma cells and in a genetically defined murine model of primary glioma.
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OLIG2 is known to regulate progenitor self-renewal at earlier developmental stages and is a master regulator for oligodendrocyte lineage specification in the ventral telencephalon.
“This is an interesting finding given that OLIG2 is known to regulate progenitor self-renewal at earlier developmental stages and is a master regulator for oligodendrocyte lineage specification in the ventral telencephalon44,45.”
From Single-cell brain organoid screening identifies developmental defects in autism (2023) · cites this paper as [45]
The Introduction (page unavailable) says Olig2 sustains progenitor replication competence, is required for optimal proliferation in embryonic forebrain neurospheres, and later helps specify oligodendrocyte progenitors. The Results (page unavailable) also report that disrupting Olig2 nearly abolishes the oligodendrocyte lineage. Our copy does not establish the claim’s specific location, the ventral telencephalon, for that lineage-specification role. (LLM, conf=0.84)
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- Authors
- Sun, Y., Meijer, D. H., Alberta, J. A., Mehta, S., Kane, M. F., Tien, A.-C., Fu, H., Petryniak, M. A., Potter, G. B., Liu, Z., Powers, J. F., Runquist, I. S., Rowitch, D. H., & Stiles, C. D.
- Affiliations
- Harvard University (US)
- Howard Hughes Medical Institute (US)
- Tufts Medical Center (US)
- Corresponding author
- Rowitch, David H.
- Stiles, Charles D.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 69
- Issue
- 5
- Pages
- 906-917
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3065213
- OpenAlex
- W2049530893
- Cited by
- 116
- References
- 5
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 4 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 7 · 2019: 3 · 2018: 6 · 2017: 6 · 2016: 11 · 2015: 7 · 2014: 20 · 2013: 10 · 2012: 11
- FWCI
- 4.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Neurological Disorders and Stroke (F32NS055631, K08NS062744, R01NS057727, NS057727, NS040511, R01NS040511)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Keywords
- Olig2, phosphorylation, neural progenitor proliferation, bHLH transcription factors, oligodendrocyte lineage, glioma, primary glioma, cell cycle exit
- MeSH terms
- Oligodendrocyte Transcription Factor 2, Analysis of Variance, Animals, Humans, Nerve Tissue Proteins, Oligodendroglia, Phosphorylation, Blotting, Western, Cell Lineage, Reverse Transcriptase Polymerase Chain Reaction, Chromatin Immunoprecipitation, Cell Proliferation, Mice, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Neural Stem Cells
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