Adenomatous polyposis coli regulates oligodendroglial development

Jordan Lang, Yoshiko Maeda, Peter Bannerman, Jie Xu, Makoto Horiuchi, David E Pleasure, Fuzheng Guo

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

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 datasuggested 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.

Original languageEnglish (US)
Pages (from-to)3113-3130
Number of pages18
JournalJournal of Neuroscience
Volume33
Issue number7
DOIs
StatePublished - Feb 13 2013

ASJC Scopus subject areas

  • Neuroscience(all)

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