Oligodendroglial Defects during Quakingviable Cerebellar Development

• Type of Material: Article
• Authors: Kenneth R Myers, Emory University; Guanglu Liu, Emory University; Yue Feng, Emory University; James Zheng, Emory University
• Language: English
• Date: 2016-09-01
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Wiley Periodicals, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1002/dneu.22369
• Title of Journal or Parent Work: Developmental Neurobiology
• ISSN: 1932-8451
• Volume: 76
• Issue: 9
• Start Page: 972
• End Page: 982
• Grant/Funding Information: This research was supported in part by grants from the National Institutes of Health to JQZ (GM083889 and MH104632), and YF (NS070526 and NS093016), and an F32 fellowship to KRM (NS092342).
• Keywords: PROTEOLIPID PROTEIN; IN-VITRO; PROGENITOR CELLS; Neurosciences; MYELIN; Bergmann glia; Quaking I; VIABLE MICE; MESSENGER-RNAS; Neurosciences & Neurology; BERGMANN GLIA; Developmental Biology; Life Sciences & Biomedicine; RNA-BINDING PROTEIN; quakingviable; oligodendroglia; MUTANT MICE; cerebellum; CENTRAL-NERVOUS-SYSTEM; Science & Technology
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Medicine and Surgery

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.