Abstract
Forkhead transcription factor family O (FoxO) maintains adult stem cell reserves by supporting their long-term proliferative potential. MicroRNAs (miRs) regulate neuronal stem/progenitor cell (NSPC) proliferation and differentiation during neural development by controlling the expression of a specific set of target genes. In the neurogenic subventricular zone, FoxO1 is specifically expressed in NSPCs and is no longer detected during the transition to neuroblast stage, forming an inverse correlation with miR-9 expression. The 3′-untranslated region of FoxO1 contains a conserved target sequence of miR-9 and FoxO1 expression is coordinated in concert with miR-9 during neuronal differentiation. Our study demonstrates that FoxO1 contributes to NSPC fate decision through its cooperation with the Notch signaling pathway.
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Abbreviations
- FoxO:
-
Forkhead transcription factor O
- miRs:
-
microRNAs
- NSPC:
-
neural stem/progenitor cells
- SVZ:
-
subventricular zone
- DCX:
-
doublecortin
- GFAP:
-
glial fibrillary acidic protein
- UTR:
-
untranslated regions
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Acknowledgements
We thank Ms Rujuta Narukar for performing IHC-RISH. This work was supported by the Ellison Medical Foundation (AG-NS-0646-10 to JP), and the Sidney Kimmel foundation (SKF-092 to JP) and National Institutes of Health Grant AG048284 (to JP).
Author contributions
D-YK, IH, FLM and J-HP performed experiments; D-YK, IH and J-HP designed experiments, analyzed data and wrote the manuscript.
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Kim, DY., Hwang, I., Muller, F. et al. Functional regulation of FoxO1 in neural stem cell differentiation. Cell Death Differ 22, 2034–2045 (2015). https://doi.org/10.1038/cdd.2015.123
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DOI: https://doi.org/10.1038/cdd.2015.123
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