Canonical Wnt signaling in the oligodendroglial lineage-puzzles remain

Fuzheng Guo, Jordan Lang, Jiho Sohn, Elizabeth Hammond, Marcello Chang, David E Pleasure

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


The straightforward concept that accentuated Wnt signaling via the Wnt-receptor-β-catenin-TCF/LEF cascade (also termed canonical Wnt signaling or Wnt/β-catenin signaling) delays or blocks oligodendrocyte differentiation is very appealing. According to this concept, canonical Wnt signaling is responsible for remyelination failure in multiple sclerosis and for persistent hypomyelination in periventricular leukomalacia. This has given rise to the hope that pharmacologically inhibiting this signaling will be of therapeutic potential in these disabling neurological disorders. But current studies suggest that Wnt/β-catenin signaling plays distinct roles in oligodendrogenesis, oligodendrocyte differentiation, and myelination in a context-dependent manner (central nervous system regions, developmental stages), and that Wnt/β-catenin signaling interplays with, and is subjected to regulation by, other central nervous system factors and signaling pathways. On this basis, we propose the more nuanced concept that endogenous Wnt/β-catenin activity is delicately and temporally regulated to ensure the seamless development of oligodendroglial lineage cells in different contexts. In this review, we discuss the role Wnt/β-catenin signaling in oligodendrocyte development, focusing on the interpretation of disparate results, and highlighting areas where important questions remain to be answered about oligodendroglial lineage Wnt/β-catenin signaling.

Original languageEnglish (US)
Pages (from-to)1671-1693
Number of pages23
Issue number10
StatePublished - Oct 1 2015


  • BMP/TGF-β
  • Canonical Wnt signaling
  • Differentiation
  • Hypoxia inducible factor
  • Myelination
  • Oligodendrocyte development
  • Regeneration
  • Remyelination
  • Signaling
  • TCF7l2 (TCF4)
  • Wnt/β-catenin signaling

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology


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