FoxOs Cooperatively Regulate Diverse Pathways Governing Neural Stem Cell Homeostasis

Paik, J. H., Ding, Z. H., Narurkar, R., Ramkissoon, S., Muller, F., Kamoun, W. S., Chae, S. S., Zheng, H. W., Ying, H. Q., Mahoney, J., Hiller, D., Jiang, S., Protopopov, A., Wong, W. H., Chin, L., Ligon, K. L., DePinho, R. A. (November 2009) FoxOs Cooperatively Regulate Diverse Pathways Governing Neural Stem Cell Homeostasis. Cell Stem Cell, 5 (5). pp. 540-553. ISSN 1934-5909

Abstract

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.

Item Type:	Paper
Uncontrolled Keywords:	FORKHEAD TRANSCRIPTION FACTORS SELF-RENEWAL OXIDATIVE STRESS ADULT NEUROGENESIS DOWN-REGULATION IN-VIVO DIFFERENTIATION PROLIFERATION FOREBRAIN BRAIN Cell & Tissue Engineering Cell Biology
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > Akt bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > phosphoinositide 3-kinase organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
CSHL Authors:	Zheng, Hongwu
Communities:	CSHL labs > Zheng lab
Depositing User:	Matt Covey
Date:	November 2009
Date Deposited:	22 Aug 2014 19:12
Last Modified:	22 Aug 2014 19:12
PMCID:	PMC3285492
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/30703

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