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Publication : Hes1 but not Hes5 regulates an astrocyte versus oligodendrocyte fate choice in glial restricted precursors.

First Author  Wu Y Year  2003
Journal  Dev Dyn Volume  226
Issue  4 Pages  675-89
PubMed ID  12666205 Mgi Jnum  J:82774
Mgi Id  MGI:2655020 Doi  10.1002/dvdy.10278
Citation  Wu Y, et al. (2003) Hes1 but not Hes5 regulates an astrocyte versus oligodendrocyte fate choice in glial restricted precursors. Dev Dyn 226(4):675-89
abstractText  To determine the role of Hes genes in the differentiation process of neuroepithelial (NEP) cells to glial restricted precursor cells (GRPs) and subsequently GRPs to oligodendrocytes and astrocytes, we have examined the effects of Hes1 and Hes5 on glial differentiation. We find that both Hes1 and Hes5 are expressed by GRPs and that Hes1 can drive GRPs to an astrocyte cell fate at the expense of oligodendrocyte differentiation. Overexpression of Hes1 in GRPs results in the up-regulation of the astrocyte markers glial fibrillary acidic protein and CD44 and the down-regulation of oligodendrocyte markers myelin proteolipid protein/DM20, GalC, and CNPase. Transcription factors involved in oligodendrocyte differentiation, such as Nkx2.2, Olig1, and Mash1, are also down-regulated in Hes1-overexpressing cells. The effect of Hes1 on gliogenesis is stage-specific as Hes1 does not direct NEP cells to an astrocytic fate. In contrast to Hes1, Hes5 does not promote astrocyte differentiation. Instead, it inhibits both astrocyte and oligodendrocyte differentiation. Overexpression of Notch1 has an effect on gliogenesis similar to that of Hes1 and the mRNA levels of Hes1 are up-regulated in cells overexpressing Notch1, suggesting that Notch1 could be an upstream activator of Hes1. Developmental Dynamics 675-689, 2003.
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