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Cited by 459FOXO transcription factor regulationNeurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene Regulation

FoxOs Cooperatively Regulate Diverse Pathways Governing Neural Stem Cell Homeostasis

Open access
Paik, Ji-hye, Ding, Zhihu, Narurkar, Rujuta, Ramkissoon, Shakti, Muller, Florian, Kamoun, Walid S., Chae, Sung-Suk, Zheng, Hongwu +9 more·2009·Cell Stem Cell
DOI 10.1016/j.stem.2009.09.013PMC PMC3285492
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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.

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Crossref · 10.1016/j.stem.2009.09.013

Cites

54 of 54 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

0 of 24 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Integrated analyses confirmed 8 bona fide novel FoxO direct targets: ASPM, TMEFF2, SIRT2, KITL, TSPAN7, sFRP1/2, and SOST.

    “these integrated analyses and highly stringent criteria confirmed 8 bona fide novel FoxO direct targets (ASPM, TMEFF2, SIRT2, KITL, TSPAN7, sFRP1/2, and SOST)”
    Quote in the paperSubstantial claim
  • Findingown data

    Knowledge-based pathway analysis showed convergent regulation of FoxO networks such as IGF-1/PI3K/PTEN, cell cycle, and metabolic pathways.

    “knowledge-based pathway analysis showed convergent regulation of well-known FoxO networks such as IGF-1/PI3K/PTEN, cell cycle and metabolic pathways”
    Quote in the paperSubstantial claim
  • Findingown data

    Early passage (P2) FoxO null NSC cultures have increased proliferation as measured by Ki67 expression and population doubling.

    “Ki67 expression (Figure 1D) and population doubling (Figure 4A) in NSC cultures revealed that early passage (P2) FoxO null NSC cultures had increased proliferation.”
    Quote in the paperSubstantial claim
  • Findingown data

    Transcriptomic analysis of multiple independent FoxO WT and null early passage neurosphere cultures revealed differential regulation of 3425 genes by FoxOs using two independent statistical methods.

    “Transcriptomic analysis of multiple independent FoxO WT and null early passage neurosphere cultures revealed differential regulation of 3425 genes by FoxOs as determined by two independent statistical methods”
    Quote in the paperSubstantial claim
  • Findingown data

    15-week-old FoxO null brains show a significant 25% decline in Sox2-positive cells in the SVZ (1 vs 0.757, p=0.004).

    “15 week-old FoxO null brain shows a significant 25% decline in Sox2-positive cells in the SVZ (Figure 2A; gray bars, 1 vs 0.757, p=0.004).”
    Quote in the paperSubstantial claim
  • May combine two claims. 28
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 11

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    Findingown data

    Late passage (P7) NAC-treated or SESN3-transduced FoxO null NSC show improved BrdU incorporation (0.09 vs 0.21, p<0.01), decreased apoptosis, and increased neurosphere diameter.

    “the late passage (P7) of NAC-treated or SESN3-transduced FoxO null NSC showed improved proliferation as measured by BrdU incorporation (Figure 3B and D; 0.09 vs 0.21, p<0.01), decreased apoptosis (Figure 4D), and increased overall neurosphere diameter”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    NSC with ASPM knockdown show decreased neurosphere size and self-renewal potential in single cell clonogenic assays (95.4 vs 48.2 and 54.1 μm, p<0.01; 1.6% vs 0 and 0.3%, p<0.05), associated with increased cell cycle exit and differentiation.

    “NSC with ASPM knockdown exhibited significant decrease in size of neurospheres and self-renewal potential in single cell clonogenic assays (Figure 5G and Supplemental Figure S6e; 95.4μm vs 48.2μm and 54.1μm in average diameter, p<0.01 and 1.6% vs 0 and 0.3% for self-renewal, p<0.05), a phenotype associated with increased cell cycle exit and differentiation”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    FoxO null cultures show reduced BrdU incorporation (0.2 vs 0.07, p=0.03) and reduced average neurosphere diameter (90.3 μm vs 61.4 μm, p=0.0043).

    “FoxO null cultures exhibited significant reduction in proliferation by BrdU incorporation (Figure 2C; 0.2 vs 0.07, p=0.03) and in average diameter of neurospheres (Figure 2C; Supplemental Figure S6a; 90.3μm vs 61.4μm, p=0.0043).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Acute in vitro deletion of all three FoxOs using Rosa26-CreERT2 decreases self-renewal capacity (3.9% vs 1.9%, p=0.096), neurosphere diameter (157.8 vs 98.6 μm, p<0.0001), and BrdU incorporation (0.38 vs 0.16, p=0.010).

    “acute in vitro deletion of all three FoxOs using the transiently 4OHT-activated Rosa26-CreERT2 system resulted in a same decrease in self-renewal capacity (Figure 2D; 3.9% vs 1.9%, p=0.096) along with decreased average diameter of neurospheres (Figure 2D; Supplementary Fig. S6b; 157.8μm vs 98.6μm, p<0.0001) and proliferation as per BrdU incorporation (Figure 2D; 0.38 vs 0.16, p=0.010).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Within the ventricular zone, FoxO1 expression is highest in Nestin-positive radial glial progenitors of the dorso-medial wall, while FoxO3 is expressed more broadly.

    “Within the VZ, FoxO1 expression is somewhat restricted with the highest level of expression noted in Nestin-positive radial glial progenitors of the dorso-medial wall of the VZ; in contrast, FoxO3 is expressed more broadly throughout all regions of the VZ examined”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Hypertrophic astrocytes are detected only in older FoxO null animals (>32 weeks) and in vitro differentiated cultures from late-passage FoxO null NSC.

    “we detected the presence of hypertrophic astrocytes only in older FoxO null animals (>32 week) and in vitro differentiated culture from late passage FoxO null NSC”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Continued passage of FoxO null NSC cultures leads to exhaustion of neurosphere formation potential, decreased proliferation, and marginally increased apoptosis.

    “continued passage in culture showed exhaustion of neurosphere formation potential with accompanying decreased proliferation and marginally increased apoptosis”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In early passage FoxO null NSC, NAC treatment up to 5 mM has no effect on transient hyper-proliferation or on proliferation of FoxO WT NSC (0.295 vs 0.294, p=0.966, P2).

    “in the early passage FoxO null NSC, NAC treatment (up to 5mM) had no effect on the transient hyper-proliferation phenotype nor did it affect the proliferation of FoxO WT NSC (Figure 4B; con vs NAC, 0.295 vs 0.294, p=0.966, P2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    FoxO null brains show progressive ventricular dilation and thinning of the lateral ventricular wall and SVZ (100% vs 751.1%, p=0.011).

    “the FoxO null brain shows consistent and progressive ventricular dilation and thinning of the lateral ventricular wall and SVZ (Supplemental Figure S4a and b; 100% vs 751.1%, p=0.011)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Many potential novel FoxO targets relate to cell cycle and glial differentiation and functionally interact with FoxOs.

    “many potential novel FoxO targets that relate well to our biological observations including cell cycle (e.g., G two and S phase expressed1, Cdk inhibitor 1C, Sal like2) and glial differentiation (e.g., Hes5, Sox10, Myelin basic protein, Plp1, Cystatin C) and that functionally interact with FoxOs (e.g. FoxG1, Sirt2)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    15-week-old FoxO null brains show declines in DCX-positive cells (1 vs 0.283, p=0.0039) and Ki67-positive cells (1 vs 0.717, p=0.026).

    “there was an accompanying decline in doublecortin (DCX, Figure 2B; gray bars, 1 vs 0.283, p=0.0039) and Ki67 (Figure 2B; gray bars, 1 vs 0.717, p=0.026) positive cells”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Both FoxO null and sFRP1/2 and SOST knockdown neural stem cells showed increased basal proliferation.

    “both FoxO null and sFRP1/2 and SOST knockdown NSC showed increased basal proliferation”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The Wnt3a-induced proliferative response is short-lived and followed by a substantial decline in the number of cycling cells, resembling the growth kinetics of FoxO null neural stem cell culture.

    “the Wnt3a-induced proliferative response is short-lived and is followed by substantial decline in number of cycling cells, resembling the growth kinetics of FoxO null NSC culture (Figure 6G).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    Combined knockdown of sFRP1/2 and SOST increased Wnt3a-induced reporter activity by 1.5-fold.

    “Combined knockdown of all three sFRP1/2 and SOST resulted in a 1.5-fold increase in Wnt3a-induced reporter activity”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Loss of all three FoxOs in HSCs decreases expression of ROS-detoxifying enzymes β-catalase and MnSOD, and increased ROS in FoxO null HSCs is causally linked to enhanced G0 exit, apoptosis, and progressive depletion of HSC reserves.

    “We have previously reported that loss of all three FoxOs in HSC results in decreased expression of ROS-detoxifying enzymes, β-catalase and MnSOD, and that increased intracellular ROS levels in FoxO null HSC are causally linked to enhanced G0 exit and increased apoptosis, resulting in progressive depletion of HSC reserves (Tothova et al., 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Tothova et al., 2007 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Newly generated neuroblasts in the SVZ migrate to the olfactory bulb, and those in the SGZ migrate into the dentate gyrus granule cell layer, affecting memory and behavior.

    “Newly generated neuroblasts in the SVZ migrate to become granule and periglomerular neurons in the olfactory bulb and neurons born in the SGZ migrate into the granule cell layer of the DG and. become dentate granule cells, contributing to the maintenance and reorganization of the existing circuitry and affecting memory and behavior (Imayoshi et al., 2008; reviewed in Zhao et al., 2008).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Imayoshi et al., 2008 source

      Not checked in the free run.

    • cites Zhao et al., 2008 source

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  • May combine two claims.

    Interpretationown data

    FoxOs regulate proliferative and self-renewal potential of NSC, and loss of FoxO function results in progressive decline of NSC number.

    “Together, these findings suggest that FoxOs regulate the proliferative and self-renewal potential of NSC and that the loss of FoxO function results in the progressive decline of NSC number.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Mammalian FoxO transcription factors act downstream of PI3K-AKT and control genes involved in proliferation, survival, metabolism, differentiation, and oxidative defense.

    “the mammalian FoxO family of transcription factors (FoxO1, 3 and 4, hereafter referred collectively as ‘FoxOs’) also act as key downstream effectors of PI3K-AKT pathway and function to control many genes governing various cellular processes such as proliferation, survival, metabolism, differentiation, and oxidative defense”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Greer and Brunet, 2005

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    ASPM is a determinant of human cerebral cortical size; individuals with ASPM germline loss-of-function mutations show primary microcephaly.

    “In humans, ASPM is a determinant of human cerebral cortical size, i.e., individuals with ASPM germline loss-of-function mutations show primary microcephaly (Bond et al., 2002).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bond et al., 2002 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    FoxOs regulate distinct sets of gene targets depending on cell type, tissue context, and developmental stage.

    “the FoxOs have been shown to regulate distinct sets of gene targets depending on cell type, tissue context and developmental stage (Paik et al., 2007; Tothova et al., 2007).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Paik et al., 2007 source

      Not checked in the free run.

    • cites Tothova et al., 2007 source

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  • May combine two claims.

    Interpretationown data

    FoxOs constrain cycling of NSC and/or progenitor cells but not their size.

    “Together, these observations suggest that FoxOs function to constrain the cycling of NSC and/or progenitor cells, but not their size”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    ASPM expression is required for symmetric, proliferative divisions of neural stem/progenitor cells of the mammalian brain.

    “ASPM expression has been shown to be required for symmetric, proliferative divisions of neural stem/progenitor cells of the mammalian brain (Fish et al., 2006; Horvath et al., 2006).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Fish et al., 2006 source

      Not checked in the free run.

    • cites Horvath et al., 2006 source

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  • May combine two claims.

    Premiseown data

    FoxOs function redundantly to promote stability of long-lived cells such as thymocytes and endothelial cells and to maintain hematopoietic stem cell reserves.

    “Recent studies from our group have underscored that the mammalian FoxOs function redundantly to promote the stability of long-lived cells such as thymocytes and endothelial cells and to maintain hematopoietic stem cell (HSC) reserves”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In adult mice, relatively quiescent neural stem cells give rise to transit-amplifying progenitors that divide rapidly and contribute to neuroblasts.

    “In adult mice, relatively quiescent NSC give rise to transit-amplifying progenitor cells which rapidly divide and contribute to neuroblasts (Morshead et al., 1994; reviewed in Zhao et al., 2008).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Morshead et al., 1994 source

      Not checked in the free run.

    • cites Zhao et al., 2008 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    FoxO-directed regulation of intracellular ROS plays an important role in NSC self-renewal capacity but no discernable role in controlling NSC proliferation activity.

    “Together, these studies suggest that, while FoxO-directed regulation of intracellular ROS level plays an important role in NSC self renewal capacity, it plays no discernable role in controlling the proliferation activity of the NSC.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    FoxOs function to support NSC homeostasis in vivo, perhaps by preventing rapid amplification of progenitors and consequent exhaustion of relatively quiescent NSC.

    “Thus, we propose that the FoxOs function to support NSC homeostasis in vivo, perhaps by preventing the rapid amplification of progenitors and the consequent exhaustion of the relatively quiescent NSC.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    FoxOs constrain proliferative activity of NSC and/or progenitor cells in the young adult brain and in early passage cultures.

    “Thus, FoxOs constrain the proliferative activity of NSC and/or progenitor cells in the young adult brain and in early passage cell cultures.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    These observations reinforce cross talk between FoxO and Wnt signaling pathways in neural stem cells and the importance of finely tuned Wnt pathway activation for long-term neural stem cell homeostasis.

    “These observations further reinforce the cross talk between FoxO and Wnt signaling pathways in NSC and the importance of finely-tuned Wnt pathway activation in the long-term homeostasis of NSC.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Functional redundancy among FoxOs exists in other tissues.

    “Consistent with functional redundancy among FoxOs in other tissues (Paik et al., 2007)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Paik et al., 2007 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Other tumor suppressors such as p16Ink4a suppress cancer at the cost of tissue resident stem cells and may contribute to decreased regenerative potential during aging.

    “other tumor suppressors (e.g., p16Ink4a) which appear to suppress cancer at the cost of tissue resident stem cells and therefore may contribute to decreased regenerative potential during the aging process (Krishnamurthy et al., 2006; Molofsky et al., 2006).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Krishnamurthy et al., 2006 source

      Not checked in the free run.

    • cites Molofsky et al., 2006 source

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  • May combine two claims.

    Interpretationown data

    FoxOs enforce neural stem cell quiescence and control neural stem cell self-renewal.

    “establishes a role for FoxOs in the enforcement of NSC quiescence and control of NSC self-renewal.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    All experimental and control animals were littermates or age matched.

    “All experimental and control animals were littermates or age matched.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    FoxOs have a role in cellular fate determination in myogenesis and hematopoiesis.

    “previously reported role for FoxOs in cellular fate determination observed in myogenesis and hematopoiesis (Hu et al., 2008; Kitamura et al., 2007; Tothova et al., 2007).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Hu et al., 2008

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    • cites Kitamura et al., 2007 source

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    • cites Tothova et al., 2007 source

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  • May combine two claims.

    Study design and conductown data

    Wnt3a, but not Wnt5a, induces TCF/Lef/β-catenin-dependent transcriptional activity, confirming specificity of the TOFlash reporter for canonical Wnt signaling.

    “Addition of Wnt3a, but not Wnt5a, induced TCF/Lef/β-catenin dependent transcriptional activity confirming the specificity of reporter activity responsive to the canonical Wnt signaling.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Loss of PTEN results in sustained proliferative potential of neural stem cells.

    “loss of the negative regulator PTEN was shown to result in sustained proliferative potential of NSC (Groszer et al., 2006; Groszer et al., 2001).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Groszer et al., 2006 source

      Not checked in the free run.

    • cites Groszer et al., 2001 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    FoxO regulates ROS detoxification, Wnt signaling, cell cycle, and differentiation processes.

    “FoxO regulates ROS detoxification, Wnt signaling, cell cycle, and differentiation processes”
    Quote in the paperSubstantial claim
36 of 36

  • The paper relies on this without support.

    Wnt signaling is essential for tissue stem cell renewal.

    “while Wnt signaling is clearly essential for tissue stem cell renewal”
1 of 1

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In mouse HSCs and neural stem cells, excessive cellular ROS concentrations cause abnormal proliferation, malignancy, and compromised self-renewal.

    “in HSCs and neural stem cells (NSCs) of mice, excessive cellular ROS concentrations lead to abnormal proliferation, malignancy and compromised stem cell self-renewal11–14”

    From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [14]

  • Similar effects occur in NSCs of FoxO-deficient mice and in HSCs and NSCs of mice lacking only FoxO3.

    “Similar results have been reported for NSCs in these FoxO-deficient mice14 and in HSCs and NSCs in mice lacking only FoxO3 (refs. 16–18).”

    From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [14]

  • Combined conditional deletion of Foxo1, Foxo3, and Foxo4 in adult neural stem/progenitor cells correlates with abnormal morphological features of differentiated neurons.

    “combined conditional deletion of genes coding for FOXO (forkhead box, sub‐group O; Foxo1, Foxo3, and Foxo4) in adult neural stem/progenitor cells correlates with abnormal morphological features of differentiated neurons (Paik et al, 2009).”

    From Autophagy in major human diseases (2021) · cites this paper as Paik et al, 2009

  • FOXO transcription factors integrate growth factors and stress signal transduction pathways, and may represent a hub for the action of various systemic factors in stem cells in ageing brain, muscle, blood and intestine.

    “For example, FOXO transcription factors integrate growth factors and stress signal transduction pathways, and may represent a ‘hub’ for the action of various systemic factors in stem cells in ageing brain, muscle, blood and intestine32,85–90.”

    From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [87]

  • Constitutive deletion of three of the FOXO genes (FOXO1, FOXO3 and FOXO4) in the MuSC lineage during development results in the impairment of postnatal establishment of the MuSC population and a more rapid MuSC depletion with age.

    “Consistent with previous reports of the role of FOXO factors in HSC, MuSC and NSC quiescence85–90, constitutive deletion of three of the FOXO genes (FOXO1, FOXO3 and FOXO4) in the MuSC lineage during development results in the impairment of postnatal establishment of the MuSC population and a more rapid MuSC depletion with age32.”

    From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [87]

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Authors
Paik, J.-H., Ding, Z., Narurkar, R., Ramkissoon, S., Muller, F., Kamoun, W. S., Chae, S.-S., Zheng, H., Ying, H., Mahoney, J., Hiller, D., Jiang, S., Protopopov, A., Wong, W. H., Chin, L., Ligon, K. L., & DePinho, R. A.
Affiliations
  • Harvard University (US)
  • Stanford University (US)
Corresponding author
DePinho, Ronald A.
ORCID
Venue
Cell Stem Cell
Publisher
Elsevier BV
Published
2009-11
Volume
5
Issue
5
Pages
540-553
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
DOI
10.1016/j.stem.2009.09.013
PMC
PMC3285492
OpenAlex
W1965306647
Cited by
459
References
54
Citations by year
2026: 8 · 2025: 12 · 2024: 23 · 2023: 27 · 2022: 23 · 2021: 35 · 2020: 34 · 2019: 16 · 2018: 35 · 2017: 32 · 2016: 28 · 2015: 31 · 2014: 24 · 2013: 43 · 2012: 32
FWCI
11.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
Funders
  • Ellison Medical Foundation
  • Damon Runyon Cancer Research Foundation
  • American Brain Tumor Association
  • Barr Foundation
  • National Cancer Institute (5P01CA95616, P01CA095616)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
FOXO transcription factors, FOXO1, FOXO3, FOXO4, neural stem cells, neural progenitor cells, PI3K/Akt signaling, brain size, neurogenesis, cell proliferation, cell differentiation, antioxidant defense, gene expression regulation, lifespan regulation
MeSH terms
Animals, Brain, Calmodulin-Binding Proteins, Cell Differentiation, Cells, Cultured, Nerve Tissue Proteins, Organ Size, Oxygen, Signal Transduction, Reactive Oxygen Species, Mice, Knockout, Gene Expression Regulation, Developmental, RNA, Small Interfering, Multipotent Stem Cells, Cell Proliferation, Wnt Proteins, Mice, Forkhead Transcription Factors, Neurogenesis

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