QKI expression is regulated during neuron-glial cell fate decisions.
QKI proteins are expressed by differentiated glia and have been implicated as regulators of myelination, but are also thought to function during early neural development. This study shows that QKI proteins are expressed in neural progenitors of the ventricular zone (vz) during murine CNS development, but that their expression is down-regulated during neuronal differentiation. By contrast, neural progenitors located in specific subdomains of the vz maintain expression of QKI proteins as they differentiate and migrate away into the emerging nervous system. These QKI+ cells have characteristics consistent with the acquisition of a glial rather than neuronal fate; they express nestin, incorporate BrdU, fail to express neuronal markers, and similar QKI+ cells are found in the postnatal subventricular zone, a known area of gliogenesis. In vitro, neural progenitor cells also down-regulate QKI expression as they differentiate into neurons, but not if they differentiate into glia. Furthermore, neural progenitors in strictly delineated subdomains of the vz dramatically up-regulate expression of the QKI-5 isoform prior to the emergence of QKI+ cells from these regions. Taken together, these data indicate that (1) glia are generated from subsets of neural progenitors found in specific, identifiable subdomains of the vz (2) QKI expression is regulated as neural progenitors undergo the neuron-glial cell fate decision and (3) QKI expression is a characteristic of glial progenitors.
Hardy
R J
RJ
Brookdale Center for Developmental and Molecular Biology, Mount Sinai Medical School, New York, New York, USA.
D000818:Animals; D018236:Carcinoma, Embryonal; D002454:Cell Differentiation; D002490:Central Nervous System / Q000196:embryology* / Q000254:growth & development; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D051379:Mice; D008959:Models, Neurological; D009457:Neuroglia / Q000737:chemistry / Q000166:cytology*; D009474:Neurons / Q000737:chemistry / Q000166:cytology*; D020033:Protein Isoforms / Q000032:analysis; D016601:RNA-Binding Proteins / Q000032:analysis*; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D020033:Protein Isoforms; C098217:Qk protein, mouse; D016601:RNA-Binding Proteins