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Cited by 22Neurogenesis and neuroplasticity mechanismsWnt/β-catenin signaling in development and cancerDevelopmental Biology and Gene Regulation

G protein-coupled receptor 17 is regulated by WNT pathway during oligodendrocyte precursor cell differentiation

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Boccazzi, Marta, Macchiarulo, Giulia, Lebon, Sophie, Janowska, Justyna, Le Charpentier, Tifenn, Faivre, Valérie, Hua, Jennifer, Marangon, Davide +7 more·2023·Neurobiology of Disease
DOI 10.1016/j.nbd.2023.106315

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Abstract

Abstract G protein-coupled receptor 17 (GPR17) and the WNT pathway are critical players of oligodendrocyte (OL) differentiation acting as essential timers in developing brain to achieve fully-myelinating cells. However, whether and how these two systems are related to each under is still unknown. Of interest, both factors are dysregulated in developing and adult brain diseases, including demyelination disorders and cancer, making the understanding of their reciprocal interactions of potential importance for identifying new targets and strategies for myelin repair. Here, we examined regulatory mechanisms linking WNT signalling to GPR17 expression in OLs. We analyzed the relative expressions of mRNAs encoding GPR17 and the T cell factor/Lymphoid enhancer-binding factor-1 (TCF/LEF) transcription factors of the canonical WNT/b-CATENIN pathway in both PDGFRa+ and O4+ OLs during mouse post-natal development. In O4+ cells, Gpr17mRNA level peaked at post-natal day 14 and then decreased concomitantly to the physiological uprise of WNT tone, as shown by increasedLef1 mRNA level. The link between WNT signaling and GPR17 expression was further reinforced in vitro in primary PDGFRa+ cells and in the Oli-neu cell line. High WNT tone impaired OL differentiation and drastically reduced GPR17 mRNA and protein levels. In Oli-neu cells, we demonstrated that WNT/b-CATENIN activation represses Gpr17 promoter activity through both putative WNT response elements (WRE) and upregulation of the inhibitor of DNA-binding protein 2 (Id2). We conclude that WNT pathway influences oligodendrocyte maturation by repressing GPR17 which could have implications in pathologies characterized by dysregulations of the oligodendroglial lineage including multiple sclerosis and oligodendroglioma.

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  • The Wnt signaling pathway inhibited oligodendrocyte differentiation and maturation while exerting a negative regulatory role in myelin development.

    “In a previous study, the Wnt signaling pathway inhibited oligodendrocyte differentiation and maturation while exerting a negative regulatory role in myelin development (Boccazzi et al., 2023).”

    From Multimodal MRI combined with RNA sequencing reveals pathological signatures in the 9-month-old 3×Tg-AD mouse brain (2026) · cites this paper as Boccazzi et al., 2023

    The Abstract (p. 3) reports that high WNT tone impaired oligodendrocyte differentiation, and the Results (p. 9) link WNT activation to maturation arrest and reduced MBP expression. The Introduction (p. 3), however, says WNT’s roles in myelination depend on CNS region and developmental stage; it does not support an unqualified negative regulatory role in myelin development. (LLM, conf=0.84)

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Authors
Boccazzi, M., Macchiarulo, G., Lebon, S., Janowska, J., Le Charpentier, T., Faivre, V., Hua, J., Marangon, D., Lecca, D., Fumagalli, M., Mani, S., Abbracchio, M. P., Gressens, P., Schang, A.-L., & Van Steenwinckel, J.
Affiliations
  • Inserm (FR)
  • University of Milan (IT)
Corresponding author
Schang, Anne-Laure
ORCID
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2023-10
Volume
187
Pages
106315
ISSN
0969-9961 (ISSN-L)
DOI
10.1016/j.nbd.2023.106315
OpenAlex
W4387223571
Cited by
22
References
3
Citations by year
2026: 9 · 2025: 9 · 2024: 4
FWCI
2.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurobiology of Disease (publishedVersion, cc-by-nc-nd)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • HAL (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Fondazione Italiana Sclerosi Multipla
  • Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques
  • Università degli Studi di Milano (PSR-2018, Horizon 2020)
  • European Commission (HORIZON2020, 874721)
  • Agence Nationale de la Recherche (ANR-11-INBS, ANR-11-INBS-0011)
  • Institut National de la Santé et de la Recherche Médicale
  • Fondation Princesse Grace de Monaco
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
GPR17, Wnt signaling, oligodendrocyte differentiation, oligodendrocyte precursor cells, canonical Wnt/β-catenin pathway, TCF/LEF transcription factors, LEF1, Id2, myelination, postnatal brain development, remyelination, multiple sclerosis, oligodendroglioma, white matter injury
MeSH terms
Oligodendrocyte Precursor Cells, Animals, Cell Differentiation, Nerve Tissue Proteins, Oligodendroglia, RNA, Messenger, Receptor, Platelet-Derived Growth Factor alpha, Receptors, G-Protein-Coupled, beta Catenin, Mice, Wnt Signaling Pathway

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