Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate.
Notch1 has been shown to induce glia in the peripheral nervous system. However, it has not been known whether Notch can direct commitment to glia from multipotent progenitors of the central nervous system. Here we present evidence that activated Notch1 and Notch3 promotes the differentiation of astroglia from the rat adult hippocampus-derived multipotent progenitors (AHPs). Quantitative clonal analysis indicates that the action of Notch is likely to be instructive. Transient activation of Notch can direct commitment of AHPs irreversibly to astroglia. Astroglial induction by Notch signaling was shown to be independent of STAT3, which is a key regulatory transcriptional factor when ciliary neurotrophic factor (CNTF) induces astroglia. These data suggest that Notch provides a CNTF-independent instructive signal of astroglia differentiation in CNS multipotent progenitor cells.
Tanigaki
K
K
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida-Konoe Sakyo, 606-8501, Kyoto, Japan.
Nogaki
F
F
Takahashi
J
J
Tashiro
K
K
Kurooka
H
H
Honjo
T
T
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology; D002999:Clone Cells / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism* / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors
D020934:Ciliary Neurotrophic Factor; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; C497763:Notch1 protein, rat; D011518:Proto-Oncogene Proteins; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2