Canonical Wnt signaling in the oligodendroglial lineage--puzzles remain

Glia
Fuzheng GuoDavid Pleasure

Abstract

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 oli...Continue Reading

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