Interactions between ID and OLIG proteins mediate the inhibitory effects of BMP4 on oligodendroglial differentiation
Open accessAbstract
Bone morphogenetic protein (BMP) signaling inhibits the generation of oligodendroglia and enhances generation of astrocytes by neural progenitor cells both in vitro and in vivo. This study examined the mechanisms underlying the effects of BMP signaling on glial lineage commitment. Treatment of cultured neural progenitor cells with BMP4 induced expression of all four members of the inhibitor of differentiation (ID) family of helix-loop-helix transcriptional inhibitors and blocked oligodendrocyte (OL) lineage commitment. Overexpression of Id4 or Id2 but not Id1 or Id3 in cultured progenitor cells reproduced both the inhibitory effects of BMP4 treatment on OL lineage commitment and the stimulatory effects on astrogliogenesis. Conversely, decreasing the levels of Id4 mRNA by RNA interference enhanced OL differentiation and inhibited the effects of BMP4 on glial lineage commitment. This suggests that induction of Id4 expression mediates effects of BMP signaling. Bacterial two-hybrid and co-immunoprecipitation studies demonstrated that ID4,and to a lesser extent ID2, complexed with the basic-helix-loop-helix transcription (bHLH) factors OLIG1 and OLIG2, which are required for the generation of OLs. By contrast, ID1 and ID3 did not complex with the OLIG proteins. In addition, the OLIG and ID proteins both interacted with the E2A proteins E12 and E47. Further, exposure of cultured progenitor cells to BMP4 changed the intracellular localization of OLIG1 and OLIG2 from a predominantly nuclear to a predominantly cytoplasmic localization. These observations suggest that the induction of ID4 and ID2, and their sequestration of both OLIG proteins and E2A proteins mediate the inhibitory effects of BMP signaling on OL lineage commitment and contribute to the generation of astrocytes.
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COPs express Neu4 and genes involved in keeping oligodendrocytes undifferentiated (Sox6, Bmp4, Gpr17).
“expressed Neu4 and genes involved in keeping oligodendrocytes undifferentiated (Sox6, Bmp4 and Gpr17) (9–11)”
From Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system (2016) · cites this paper as [10]
The BMP4-inhibition results (Fig. 1; page unavailable in our copy) show that BMP4 treatment reduced oligodendrocyte-lineage cells, supporting BMP4’s inhibitory role. The paper does not establish that COPs express Neu4, Sox6, BMP4, or Gpr17, or address the roles of the other listed genes. (LLM, conf=0.86)
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- Authors
- Samanta, J., & Kessler, J. A.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Samanta, Jayshree
- Kessler, John A.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2004-09-01
- Volume
- 131
- Issue
- 17
- Pages
- 4131-4142
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2043364678
- Cited by
- 361
- References
- 69
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 12 · 2023: 12 · 2022: 15 · 2021: 16 · 2020: 11 · 2019: 17 · 2018: 10 · 2017: 12 · 2016: 14 · 2015: 20 · 2014: 20 · 2013: 28 · 2012: 22
- FWCI
- 4.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS-20778, R01NS020778)
- 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
- BMP4 signaling, oligodendrocyte differentiation, Id4, Id2, Olig1, Olig2, E2A transcription factor, E12, E47, neural progenitor cells, astrocyte differentiation, protein-protein interaction, subcellular localization
- MeSH terms
- Oligodendrocyte Transcription Factor 2, Animals, Astrocytes, Cell Differentiation, Cell Line, Cytoplasm, DNA-Binding Proteins, Humans, Immunohistochemistry, Luminescent Proteins, Microscopy, Fluorescence, Models, Biological, Nerve Tissue Proteins, Neurons, Oligodendroglia, Phenotype, Precipitin Tests, Protein Binding, RNA, Messenger, Time Factors, Transcription Factors, Transfection, Blotting, Western, Signal Transduction, Cell Lineage, Bone Morphogenetic Proteins, Reverse Transcriptase Polymerase Chain Reaction, Two-Hybrid System Techniques, RNA Interference, Green Fluorescent Proteins, Mice, Basic Helix-Loop-Helix Proteins, Basic Helix-Loop-Helix Transcription Factors, Bone Morphogenetic Protein 4
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