کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2077989 1079760 2009 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
FoxOs Cooperatively Regulate Diverse Pathways Governing Neural Stem Cell Homeostasis
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
پیش نمایش صفحه اول مقاله
FoxOs Cooperatively Regulate Diverse Pathways Governing Neural Stem Cell Homeostasis
چکیده انگلیسی

SummaryThe 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 5, Issue 5, 6 November 2009, Pages 540–553
نویسندگان
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