title: Wnt signaling is sufficient to perturb oligodendrocyte maturation.
abstract: The development of oligodendrocytes, the myelinating cells of the central nervous system, is temporally and spatially controlled by local signaling factors acting as inducers or inhibitors. Dorsal spinal cord tissue has been shown to contain inhibitors of oligodendrogliogenesis, although their identity is not completely known. We have studied the actions of one family of dorsal signaling molecules, the Wnts, on oligodendrocyte development. Using tissue culture models, we have shown that canonical Wnt activity through beta-catenin activation inhibits oligodendrocyte maturation, independently of precursor proliferation, cell death, or diversion to an alternate cell fate. Mice in which Wnt/beta-catenin signaling was constitutively activated in cells of the oligodendrocyte lineage had equal numbers of oligodendrocyte precursors relative to control littermates, but delayed appearance of mature oligodendrocytes, myelin protein, and myelinated axons during development, although these differences largely disappeared by adulthood. These results indicate that activating the Wnt/beta-catenin pathway delays the development of myelinating oligodendrocytes.
authors.affiliation: Department of Research Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Feigenson
authors.forename: Mary
authors.initials: M
authors.lastname: Reid
authors.forename: Jill
authors.initials: J
authors.lastname: See
authors.forename: E Bryan
authors.initials: EB
authors.lastname: Crenshaw
authors.forename: Judith B
authors.initials: JB
authors.lastname: Grinspan
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D051379:Mice; D008822:Mice, Transgenic; D009185:Myelin Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D009185:Myelin Proteins; D051153:Wnt Proteins; D051176:beta Catenin