title: Oligodendroglial defects during quakingviable cerebellar development.
abstract: The selective RNA-binding protein Quaking I (QKI) has previously been implicated in RNA localization and stabilization, alternative splicing, cell proliferation, and differentiation. The spontaneously-occurring quakingviable (qkv) mutant mouse exhibits a sharply attenuated level of QKI in myelin-producing cells, including oligodendrocytes (OL) because of the loss of an OL-specific promoter. The disruption of QKI in OLs results in severe hypomyelination of the central nervous system, but the underlying cellular mechanisms remain to be fully elucidated. In this study, we used the qkv mutant mouse as a model to study myelination defects in the cerebellum. We found that oligodendroglial development and myelination are adversely affected in the cerebellum of qkv mice. Specifically, we identified an increase in the total number of oligodendroglial precursor cells in qkv cerebella, a substantial portion of which migrated into the grey matter. Furthermore, these mislocalized oligodendroglial precursor cells retained their migratory morphology late into development. Interestingly, a number of these presumptive oligodendrocyte precursors were found at the Purkinje cell layer in qkv cerebella, resembling Bergman glia. These findings indicate that QKI is involved in multiple aspects of oligodendroglial development. QKI disruption can impact the cell fate of oligodendrocyte precursor cells, their migration and differentiation, and ultimately myelination in the cerebellum. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 972-982, 2016.
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, 30322.|Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, Georgia, 30322.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Myers
authors.affiliation: Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia, 30322.
authors.forename: Guanglu
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia, 30322.
authors.forename: Yue
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, 30322.|Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, Georgia, 30322.|Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, 30322.
authors.forename: James Q
authors.initials: JQ
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002526:Cerebellar Diseases / Q000378:metabolism*; D002531:Cerebellum / Q000254:growth & development / Q000502:physiology*; D003711:Demyelinating Diseases / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008821:Mice, Quaking; D008822:Mice, Transgenic; D009836:Oligodendroglia / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: C098217:Qk protein, mouse; D016601:RNA-Binding Proteins
keywords: Bergmann glia; Quaking I; cerebellum; oligodendroglia; quakingviable