FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis
By J. Paik, Z. Ding, Rujuta Narurkar, S. Ramkissoon, F. Muller, W. Kamoun, Sung-suk Chae, Hongwu Zheng, Haoqiang Ying, J. Mahoney and 7 more. 2009
451 citations recorded by the source corpus.
Summary The PI3K-AKT-FoxO pathway is integral to lifespan regulation in lower organisms and essential for the stability of long-lived cells in mammals. Here, we report the impact of combined FoxO1, 3 and 4 deficiencies on mammalian brain physiology with a particular emphasis on the study of the neural stem/progenitor cell (NSC) pool. We show that the FoxO family plays a prominent role in NSC proliferation and renewal. FoxO deficient mice show initial increased brain size and proliferation of neural progenitor cells during early postnatal life, followed by precocious significant decline in the NSC pool and accompanying neurogenesis in adult brains. Mechanistically, integrated transcriptomic, promoter and functional analyses of FoxO deficient NSC cultures identified direct gene targets with known links to the regulation of human brain size and the control of cellular proliferation, differentiation, and oxidative defense. Thus, the FoxO family coordinately regulates diverse genes and pathways to govern key aspects of NSC homeostasis in the mammalian brain.
Subfields: Aging, Molecular Biology
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- Cristina Sánchez-Ramos
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- L. Klotz
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- P. Urbánek
- H. Steinbrenner
Citations in the corpus
- FoxO3 regulates neural stem cell homeostasis (2009, unknown): “We find that adult FoxO3(-/-) mice have fewer NSCs in vivo than wild-type counterparts.”
- Redox regulation of FoxO transcription factors (2015, background): “Brain-specific ablation of FoxO3a or combined inactivation of FoxO1a/3a/4 in mice resulted in a phenotype that resembled agedependent depletion of the neural stem cell (NSC) population [290,291].”
- Linking functional decline of telomeres, mitochondria and stem cells during ageing (2010, unknown): “For example, disruption of FOXO proteins, which are key downstream components of the PI(3)K pathway, results in the ROS-induced depletion of tissue stem cell”