title: Adenomatous polyposis coli regulates oligodendroglial development.
abstract: The expression of the gut tumor suppressor gene adenomatous polyposis coli (Apc) and its role in the oligodendroglial lineage are poorly understood. We found that immunoreactive APC is transiently induced in the oligodendroglial lineage during both normal myelination and remyelination following toxin-induced, genetic, or autoimmune demyelination murine models. Using the Cre/loxP system to conditionally ablate APC from the oligodendroglial lineage, we determined that APC enhances proliferation of oligodendroglial progenitor cells (OPCs) and is essential for oligodendrocyte differentiation in a cell-autonomous manner. Biallelic Apc disruption caused translocation of β-catenin into the nucleus and upregulated β-catenin-mediated Wnt signaling in early postnatal but not adult oligodendroglial lineage cells. The results of conditional ablation of Apc or Ctnnb1 (the gene encoding β-catenin) and of simultaneous conditional ablation of Apc and Ctnnb1 revealed that β-catenin is dispensable for postnatal oligodendroglial differentiation, that Apc one-allele deficiency is not sufficient to dysregulate β-catenin-mediated Wnt signaling in oligodendroglial lineage cells, and that APC regulates oligodendrocyte differentiation through β-catenin-independent, as well as β-catenin-dependent, mechanisms. Gene ontology analysis of microarray data suggested that the β-catenin-independent mechanism involves APC regulation of the cytoskeleton, a result compatible with established APC functions in neural precursors and with our observation that Apc-deleted OPCs develop fewer, shorter processes in vivo. Together, our data support the hypothesis that APC regulates oligodendrocyte differentiation through both β-catenin-dependent and additional β-catenin-independent mechanisms.
authors: Institute for Pediatric Regenerative Medicine, University of California, Davis, School of Medicine and Shriners Hospital, Sacramento, California 95817, USA.
authors: Jordan
authors: J
authors: Lang
authors: Yoshiko
authors: Y
authors: Maeda
authors: Peter
authors: P
authors: Bannerman
authors: Jie
authors: J
authors: Xu
authors: Makoto
authors: M
authors: Horiuchi
authors: David
authors: D
authors: Pleasure
authors: Fuzheng
authors: F
authors: Guo
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D000818:Animals; D000906:Antibodies; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D002478:Cells, Cultured; D004965:Estrogen Antagonists / Q000494:pharmacology; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D018613:Microscopy, Confocal; D018992:Myelin-Associated Glycoprotein / Q000096:biosynthesis; D009416:Nerve Regeneration / Q000502:physiology; D009836:Oligodendroglia / Q000502:physiology*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D013234:Stem Cells / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology; D051176:beta Catenin / Q000502:physiology
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D000906:Antibodies; D004965:Estrogen Antagonists; D018992:Myelin-Associated Glycoprotein; D012333:RNA, Messenger; D051176:beta Catenin; D013629:Tamoxifen; D012313:RNA