Negative regulatory effect of an oligodendrocytic bHLH factor OLIG2 on the astrocytic differentiation pathway.
In the developing vertebrate nervous system, multipotent neural stem cells produce both neurons and glia. OLIG2 is a basic helix-loop-helix transcription factor that plays critical roles in oligodendrocyte and motor neuron development; however, its role in astrocytic development remains elusive. In this study, we analyzed an effect of OLIG2 on cytokine-induced astrocytic differentiation from mouse telencephalic neuroepithelial cells. We show that the presence of OLIG2 protein leads to inhibition of the promoter activation of astrocyte-specific glial fibrillary acidic protein gene. We found that OLIG2 abolishes complex formation between a transcriptional coactivator p300 and a transcription factor, signal transducer and activator of transcription 3 (STAT3), which is activated by astrocytic differentiation-inducing cytokines, such as leukemia inhibitory factor (LIF). The enforced expression of OLIG2 in neuroepithelial cells inhibits the LIF-induced astrocytic differentiation. We also show that the OLIG2 protein in the nuclei of neural precursor cells disappears in accordance with astrocytic differentiation during culture with LIF. Together, these results reveal a novel molecular function of OLIG2 on the astrocyte development. Cell Death and Differentiation (2004) 11, 196-202. doi:10.1038/sj.cdd.4401332 Published online 24 October 2003
Fukuda
S
S
Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Japan.
Kondo
T
T
Takebayashi
H
H
Taga
T
T
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D050881:E1A-Associated p300 Protein; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D000882:Haplorhini; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D021381:Protein Transport; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D050881:E1A-Associated p300 Protein; D005904:Glial Fibrillary Acidic Protein; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; C405708:OLIG2 protein, human; C512773:Olig2 protein, mouse; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; C494361:Ep300 protein, mouse