Hes1 but not Hes5 regulates an astrocyte versus oligodendrocyte fate choice in glial restricted precursors.
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.
Wu
Yuanyuan
Y
Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Liu
Ying
Y
Levine
Edward M
EM
Rao
Mahendra S
MS
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D009687:Nuclear Proteins; D009836:Oligodendroglia / Q000166:cytology* / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D000072056:Transcription Factor HES-1; D014157:Transcription Factors / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; C489735:Hes1 protein, rat; C489686:Hes5 protein, rat; C000715631:NKX2-2 protein, human; C000715628:Nkx2-2 protein, rat; C497763:Notch1 protein, rat; C077478:HES5 protein, human