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PMID:12666205

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Citation

Wu, Y, Liu, Y, Levine, EM and Rao, MS (2003) Hes1 but not Hes5 regulates an astrocyte versus oligodendrocyte fate choice in glial restricted precursors. Dev. Dyn. 226:675-89

Abstract

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.

Links

PubMed Online version:10.1002/dvdy.10278

Keywords

Animals; Astrocytes/cytology; Astrocytes/physiology; Basic Helix-Loop-Helix Transcription Factors; Cell Differentiation/physiology; Cell Lineage/physiology; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Epithelial Cells/cytology; Epithelial Cells/physiology; Female; Gene Expression Regulation, Developmental; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Oligodendroglia/cytology; Oligodendroglia/physiology; Pregnancy; Rats; Rats, Sprague-Dawley; Receptor, Notch1; Receptors, Cell Surface/genetics; Repressor Proteins/genetics; Repressor Proteins/metabolism; Spinal Cord/cytology; Spinal Cord/embryology; Spinal Cord/physiology; Stem Cells/cytology; Stem Cells/physiology; Transcription Factors/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:HES1

involved_in

GO:0048711: positive regulation of astrocyte differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HES1

involved_in

GO:0048715: negative regulation of oligodendrocyte differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HES1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:HES1

involved_in

GO:0060253: negative regulation of glial cell proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HES5

involved_in

GO:0048712: negative regulation of astrocyte differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HES5

involved_in

GO:0048715: negative regulation of oligodendrocyte differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NOTC1

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NOTC1

involved_in

GO:0048711: positive regulation of astrocyte differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NOTC1

involved_in

GO:0048715: negative regulation of oligodendrocyte differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NOTC1

involved_in

GO:0060253: negative regulation of glial cell proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:HES1

involved_in

GO:0048715: negative regulation of oligodendrocyte differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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