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

Wu Y, Liu Y, Levine EM, Rao MS
Dev Dyn. 2003 226 (4): 675-89

PMID: 12666205 · DOI:10.1002/dvdy.10278

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.

Copyright 2003 Wiley-Liss, Inc.

MeSH Terms (21)

Animals Astrocytes Basic Helix-Loop-Helix Transcription Factors Cell Differentiation Cell Lineage DNA-Binding Proteins Epithelial Cells Female Gene Expression Regulation, Developmental Homeodomain Proteins Oligodendroglia Pregnancy Rats Rats, Sprague-Dawley Receptor, Notch1 Receptors, Cell Surface Repressor Proteins Spinal Cord Stem Cells Transcription Factor HES-1 Transcription Factors

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