The wnt effector transcription factor 7-like 2 positively regulates oligodendrocyte differentiation in a manner independent of wnt/²-catenin signaling

Elizabeth Hammond, Jordan Lang, Yoshiko Maeda, David E Pleasure, Melinda Angus-Hill, Jie Xu, Makoto Horiuchi, Wenbin Deng, Fuzheng Guo

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Genetic or pharmacological activation of canonical Wnt/-catenin signaling inhibits oligodendrocyte differentiation. Transcription factor 7-like 2 (TCF7l2), also known as TCF4, is a Wnt effector induced transiently in the oligodendroglial lineage. A well accepted dogma is that TCF7l2 inhibits oligodendrocyte differentiation through activation of Wnt/-catenin signaling. We report that TCF7l2 is upregulated transiently in postmitotic, newly differentiated oligodendrocytes. Using in vivo gene conditional ablation, we found surprisingly that TCF7l2 positively regulates neonatal and postnatal mouse oligodendrocyte differentiation during developmental myelination and remyelination in a manner independent of the Wnt/-catenin signaling pathway. We also reveal a novel role of TCF7l2 in repressing a bone morphogenetic protein signaling pathway that is known to inhibit oligodendrocyte differentiation. Thus, our study provides novel data justifying therapeutic attempts to enhance, rather than inhibit, TCF7l2 signaling to overcome arrested oligodendroglial differentiation in multiple sclerosis and other demyelinating diseases.

Original languageEnglish (US)
Pages (from-to)5007-5022
Number of pages16
JournalJournal of Neuroscience
Volume35
Issue number12
DOIs
StatePublished - 2015

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Keywords

  • BMP signaling
  • Canonical wnt/beta-catenin signaling
  • Myelination
  • Oligodendrocyte differentiation
  • Remyelination
  • TCF7l2(TCF4)

ASJC Scopus subject areas

  • Neuroscience(all)

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