Sox3 expression identifies neural progenitors in persistent neonatal and adult mouse forebrain germinative zones

Abstract

Neural precursors persist throughout life in the rodent forebrain subventricular zone (SVZ) and hippocampal dentate gyrus. The regulation of persistent neural stem cells is poorly understood, in part because of the lack of neural progenitor markers. The Sox B1 subfamily of HMG-box transcription factors (Sox1-3) is expressed by precursors in the embryonic nervous system, where these factors maintain neural progenitors in an undifferentiated state while suppressing neuronal differentiation. Sox2 expression persists in germinative zones of the adult rodent brain, but Sox3 expression in the postnatal brain remains largely unexplored. Here we examine Sox3 expression in the neonatal and adult mouse brain to gain insight into its potential involvement in regulating persistent neural stem cells and neurogenesis. We also investigate Sox3 expression during expansion and neural differentiation of postnatal mouse SVZ neural stem cell and human embryonic stem cell (hESC) cultures. We find that Sox3 is expressed transiently by proliferating and differentiating neural progenitors in the SVZ-olfactory bulb pathway and dentate gyrus. Sox3 immunoreactivity also persists in specific postmitotic neuronal populations. In vitro, high Sox3 protein expression levels in undifferentiated, SVZ-derived neurospheres decline markedly with differentiation. Sox3 immunoreactivity in hESCs appears upon differentiation to neural progenitors and then decreases as cells differentiate further into neurons. These findings suggest that Sox3 labels specific stages of hESC-derived and murine neonatal and adult neural progenitors and are consistent with a role for Sox3 in neural stem cell maintenance. Persistent Sox3 expression in some mature neuronal populations suggests additional undefined roles for Sox3 in neuronal function.

NFIA Controls Telencephalic Progenitor Cell Differentiation through Repression of the Notch Effector Hes1

“…These included the Notch ligand Delta-like ligand 1 (Dll1) and the key Notch effectors Hes1 and Hey2, as well as Id4, an inhibitor of stem cell differentiation. Expression of Neurogenin 2 (Ngn2), a proneural gene known to regulate Dll1 (Castro et al, 2006), was also significantly upregulated in the mutant, as was Sox3, which has been implicated in neural stem cell maintenance (Wang et al, 2006). Validation of these array data via both in situ hybridization and qPCR (Fig.…”

Control of cell fate and differentiation by Sry-related high-mobility-group box (Sox) transcription factors

“…The three proteins counteract the functions of proneural basic helix-loop-helix transcription factors Pevny and Placzek, 2005). The SoxB1 genes continue to be expressed and to maintain neural stem cells in the adult brain, as supported by the observation that reduced expression of Sox2 in adult mice results in a loss of neuronal precursors and in neurodegeneration as observed in the Huntington and Alzheimer diseases (Ferri et al, 2004;Ekonomou et al, 2005;Wang et al, 2006;Sottile et al, 2006). Neurogenesis (development of neurons), is initiated in the embryo when proneural proteins upregulate expression of the SoxB2 genes Sox14 and Sox21 (Malas et al, 1999).…”

The role of SOX proteins in normal pituitary development

“…In neonatal and adult mouse forebrain, Sox3 expression persists in neurogenic regions that include the subventricular zone and the subgranular zone of the hippocampal dentate gyrus. Its expression is also maintained, though at lower levels, in specific non-neurogenic regions of the adult mouse brain (i.e in the cerebellar Purkinje cell layer, ventromedial hypothalamus and dorsolateral septum; Wang et al 2006). These SOX3 positive cells may represent quiescent progenitors but the significance of this expression pattern remains unknown.…”