RESUMEN
The controlling factors that prompt mature oligodendrocytes to myelinate axons are largely undetermined. In this study, we used a forward genetics approach to identify a mutant mouse strain characterized by the absence of CNS myelin despite the presence of abundant numbers of late-stage, process-extending oligodendrocytes. Through linkage mapping and complementation testing, we identified the mutation as a single nucleotide insertion in the gene encoding zinc finger protein 191 (Zfp191), which is a widely expressed, nuclear-localized protein that belongs to a family whose members contain both DNA-binding zinc finger domains and protein-protein-interacting SCAN domains. Zfp191 mutants express an array of myelin-related genes at significantly reduced levels, and our in vitro and in vivo data indicate that mutant ZFP191 acts in a cell-autonomous fashion to disrupt oligodendrocyte function. Therefore, this study demonstrates that ZFP191 is required for the myelinating function of differentiated oligodendrocytes.
Asunto(s)
Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Vaina de Mielina/metabolismo , Oligodendroglía/metabolismo , Alelos , Animales , Diferenciación Celular , Línea Celular , Proliferación Celular , Células Cultivadas , Sistema Nervioso Central/embriología , Embrión de Mamíferos/metabolismo , Ratones , Ratones Transgénicos , MutaciónRESUMEN
Intercellular signaling between the axon and myelinating glial cells plays an essential role in the regulation of the myelination process. A recent study from Monk et al. has used a forward genetics approach in zebrafish to identify a G protein-coupled receptor that is necessary for Schwann cells to myelinate axons, thereby uncovering a critical component of the axo-glial signaling network.