title: Canonical Wnt signaling in the oligodendroglial lineage--puzzles remain.
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 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.
authors.affiliation: Neurology Department, School of Medicine at UC Davis Medical Center, Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, Northern California, Sacramento, California.
authors.forename: Fuzheng
authors.initials: F
authors.lastname: Guo
authors.affiliation: Neurology Department, School of Medicine at UC Davis Medical Center, Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, Northern California, Sacramento, California.
authors.forename: Jordan
authors.initials: J
authors.lastname: Lang
authors.affiliation: Neurology Department, School of Medicine at UC Davis Medical Center, Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, Northern California, Sacramento, California.
authors.forename: Jiho
authors.initials: J
authors.lastname: Sohn
authors.affiliation: Neurology Department, School of Medicine at UC Davis Medical Center, Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, Northern California, Sacramento, California.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hammond
authors.affiliation: Neurology Department, School of Medicine at UC Davis Medical Center, Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, Northern California, Sacramento, California.
authors.forename: Marcello
authors.initials: M
authors.lastname: Chang
authors.affiliation: Neurology Department, School of Medicine at UC Davis Medical Center, Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, Northern California, Sacramento, California.
authors.forename: David
authors.initials: D
authors.lastname: Pleasure
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D009836:Oligodendroglia / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D051153:Wnt Proteins
keywords: BMP/TGF-β; TCF7l2 (TCF4); Wnt/β-catenin signaling; canonical Wnt signaling; differentiation; hypoxia inducible factor; myelination; oligodendrocyte development; regeneration; remyelination; signaling