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Cited by 210Neurogenesis and neuroplasticity mechanismsMultiple Sclerosis Research StudiesDevelopmental Biology and Gene Regulation

Notch1 signaling plays a role in regulating precursor differentiation during CNS remyelination

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Zhang, Yueting, Argaw, Azeb Tadesse, Gurfein, Blake T., Zameer, Andleeb, Snyder, Brian J., Ge, Changhui, Lu, Q. Richard, Rowitch, David H. +3 more·2009·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0902834106PMC PMC2776461
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Abstract

In the developing CNS, Notch1 and its ligand, Jagged1, regulate oligodendrocyte differentiation and myelin formation, but their role in repair of demyelinating lesions in diseases such as multiple sclerosis remains unresolved. To address this question, we generated a mouse model in which we targeted Notch1 inactivation to oligodendrocyte progenitor cells (OPCs) using Olig1 Cre and a floxed Notch1 allele, Notch1 12f . During CNS development, OPC differentiation was potentiated in Olig1 Cre:Notch1 12f/12f mice. Importantly, in adults, remyelination of demyelinating lesions was also accelerated, at the expense of proliferation within the progenitor population. Experiments in vitro confirmed that Notch1 signaling was permissive for OPC expansion but inhibited differentiation and myelin formation. These studies also revealed that astrocytes exposed to TGF-β1 restricted OPC maturation via Jagged1-Notch1 signaling. These data suggest that Notch1 signaling is one of the mechanisms regulating OPC differentiation during CNS remyelination. Thus, Notch1 may represent a potential therapeutical avenue for lesion repair in demyelinating disease.

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  • In OPCs, there was early upregulation of several transcription factors and Notch ligands known to regulate differentiation to oligodendrocytes after loss of surrounding oligodendrocytes.

    “In OPCs, there was early upregulation of several transcription factors (OLIG1, OLIG2, SOX10, SOX8, PRRX1, ASCL1) and Notch ligands (DLL1, DLL3) known to regulate differentiation78–81 to oligodendrocytes after loss of surrounding oligodendrocytes (Fig. 7e, right, and Fig. 7g).”

    From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [79]

    The Abstract (page unavailable) identifies Delta1–4 as Notch ligands, and the Results and Discussion (pages unavailable) show that Notch1 signaling regulates OPC differentiation. The paper tests Jagged1–Notch1 signaling, however; it does not establish that DLL1 or DLL3 specifically regulate differentiation. The early upregulation is presented with the citing paper’s own figures, not attributed to this source. (LLM, conf=0.82)

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Research works printed but not linked: 28

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Authors
Zhang, Y., Argaw, A. T., Gurfein, B. T., Zameer, A., Snyder, B. J., Ge, C., Lu, Q. R., Rowitch, D. H., Raine, C. S., Brosnan, C. F., & John, G. R.
Affiliations
  • Mount Sinai Hospital (US)
  • Pediatrics and Genetics (US)
  • Icahn School of Medicine at Mount Sinai (US)
  • Capital Medical University (CN)
  • The University of Texas Southwestern Medical Center (US)
  • University of California, San Francisco (US)
  • Albert Einstein College of Medicine (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2009-11-10
Volume
106
Issue
45
Pages
19162-19167
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0902834106
PMC
PMC2776461
OpenAlex
W2125573110
Cited by
210
References
4
Citations by year
2026: 5 · 2025: 10 · 2024: 14 · 2023: 6 · 2022: 11 · 2021: 12 · 2020: 12 · 2019: 16 · 2018: 8 · 2017: 15 · 2016: 10 · 2015: 10 · 2014: 14 · 2013: 21 · 2012: 11
FWCI
4.60
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5k08ca001022-03)
  • U.S. Public Health Service (95022)
  • National Cancer Institute (CA095823, R24CA095823, CA1022)
  • National Institute of Neurological Disorders and Stroke (R01NS062703, NS-08952, NS046620, R01NS046620, NS050389, NS056074, R01NS056074, NS011920, P50NS011920, NS040511, R01NS050389, R01NS008952, R01NS040511)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
Notch1 signaling, Jagged1, oligodendrocyte precursor cells, demyelinating lesions, multiple sclerosis, oligodendrocyte differentiation, myelination, OPC proliferation, astrocytes, TGF-β1, lesion repair
MeSH terms
Serrate-Jagged Proteins, Jagged-1 Protein, Animals, Calcium-Binding Proteins, Cell Differentiation, Central Nervous System, Immunohistochemistry, Membrane Proteins, Myelin Sheath, Oligodendroglia, Signal Transduction, Intercellular Signaling Peptides and Proteins, Mice, Receptor, Notch1

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