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PMID:12666205
| 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 |
| edit table |
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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