title: Zfp488 promotes oligodendrocyte differentiation of neural progenitor cells in adult mice after demyelination.
abstract: Basic helix-loop-helix transcription factors Olig1 and Olig2 critically regulate oligodendrocyte development. Initially identified as a downstream effector of Olig1, an oligodendrocyte-specific zinc finger transcription repressor, Zfp488, cooperates with Olig2 function. Although Zfp488 is required for oligodendrocyte precursor formation and differentiation during embryonic development, its role in oligodendrogenesis of adult neural progenitor cells is not known. In this study, we tested whether Zfp488 could promote an oligodendrogenic fate in adult subventricular zone (SVZ) neural stem/progenitor cells (NSPCs). Using a cuprizone-induced demyelination model in mice, we examined the effect of retrovirus-mediated Zfp488 overexpression in SVZ NSPCs. Our results showed that Zfp488 efficiently promoted the differentiation of the SVZ NSPCs into mature oligodendrocytes in vivo. After cuprizone-induced demyelination injury, Zfp488-transduced mice also showed significant restoration of motor function to levels comparable to control mice. Together, these findings identify a previously unreported role for Zfp488 in adult oligodendrogenesis and functional remyelination after injury.
authors.affiliation: Departments of Cell Biology and Human Anatomy, University of California, Davis, Sacramento, California 95817, USA.
authors.forename: Mangala M
authors.initials: MM
authors.lastname: Soundarapandian
authors.forename: Vimal
authors.initials: V
authors.lastname: Selvaraj
authors.forename: U-Ging
authors.initials: UG
authors.lastname: Lo
authors.forename: Mari S
authors.initials: MS
authors.lastname: Golub
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Feldman
authors.forename: David E
authors.initials: DE
authors.lastname: Pleasure
authors.forename: Wenbin
authors.initials: W
authors.lastname: Deng
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D003711:Demyelinating Diseases / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology*; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology*; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: D012097:Repressor Proteins; C583020:Zfp488 protein, mouse