title: The Wnt effector transcription factor 7-like 2 positively regulates oligodendrocyte differentiation in a manner independent of Wnt/β-catenin signaling.
abstract: Genetic or pharmacological activation of canonical Wnt/β-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/β-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/β-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.
authors: Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, California 95817.
authors: Elizabeth
authors: E
authors: Hammond
authors: Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, California 95817.
authors: Jordan
authors: J
authors: Lang
authors: Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, California 95817.
authors: Yoshiko
authors: Y
authors: Maeda
authors: Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, California 95817, Departments of Neurology.
authors: David
authors: http://orcid.org/0000-0002-9122-1268
authors: D
authors: Pleasure
authors: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112.
authors: Melinda
authors: M
authors: Angus-Hill
authors: Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, California 95817.
authors: Jie
authors: J
authors: Xu
authors: Pathology and Laboratory Medicine, School of Medicine, University of California, Davis, Sacramento, California 95817, and.
authors: Makoto
authors: M
authors: Horiuchi
authors: Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, California 95817, Biochemistry and Molecular Medicine, and.
authors: Wenbin
authors: W
authors: Deng
authors: Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, California 95817, Departments of Neurology, fzguo@ucdavis.edu.
authors: Fuzheng
authors: http://orcid.org/0000-0003-3410-8389
authors: F
authors: Guo
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D051379:Mice; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000235:genetics / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology* / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics / Q000502:physiology*; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; C544895:Tcf7l2 protein, mouse; D058118:Transcription Factor 7-Like 2 Protein; D051176:beta Catenin
keywords: BMP signaling; TCF7l2(TCF4); canonical Wnt/beta-catenin signaling; myelination; oligodendrocyte differentiation; remyelination