FoxOs in neural stem cell fate decision

Ro, Seung‐Hyun; Liu, Debra; Yeo, Hyeonju; Paik, Jihye

doi:10.1016/j.abb.2012.07.017

Cited by 28 publications

(16 citation statements)

References 191 publications

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“…During cortical development, FoxO6 has a regionalized expression pattern, mapping to different cortical subregions at different developmental stages, suggesting FoxO6 functions in multiple neuronal developmental processes (14). At early developmental stages (E12.5), FoxO6 is expressed in the proliferating ventricular zone (VZ) and subventricular zone (SVZ), suggesting FoxO6 may be involved in neuronal stem cell proliferation and/or stem cell maintenance, as has been suggested previously for other mammalian FoxOs (8)(9)(10). At E14.5, FoxO6 remains expressed in the VZ and SVZ and expression is now also observed in the outer layer of the cortical plate (CP) (14).…”

Section: Resultsmentioning

confidence: 90%

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FoxO6 affects Plxna4-mediated neuronal migration during mouse cortical development

Paap

Oosterbroek

Wagemans

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The forkhead transcription factor FoxO6 is prominently expressed during development of the murine neocortex. However, its function in cortical development is as yet unknown. We now demonstrate that cortical development is altered in FoxO6 +/− and FoxO6 −/− mice, showing migrating neurons halted in the intermediate zone. Using a FoxO6-directed siRNA approach, we substantiate the requirement of FoxO6 for a correct radial migration in the developing neocortex. Subsequent genome-wide transcriptome analysis reveals altered expression of genes involved in cell adhesion, axon guidance, and gliogenesis upon silencing of FoxO6. We then show that FoxO6 binds to DAF-16-binding elements in the Plexin A4 (Plxna4) promoter region and affects Plxna4 expression. Finally, ectopic Plxna4 expression restores radial migration in FoxO6 +/− and siRNA-mediated knockdown models. In conclusion, the presented data provide insights into the molecular mechanisms whereby transcriptional programs drive cortical development.

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Section: Resultsmentioning

confidence: 90%

“…Recent studies have shown that FoxOs are required for the coordinated regulation of postnatal neuronal stem cell (NSC) homeostasis, demonstrating a prominent role for FoxO3 in NSC proliferation and renewal (8)(9)(10). In a combined FoxO1,3,4-deficient mouse model, an initial increase in brain size was observed followed by a decline in the adult NSC pool.…”

mentioning

confidence: 97%

FoxO6 affects Plxna4-mediated neuronal migration during mouse cortical development

Paap

Oosterbroek

Wagemans

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…S100b-immunoreactive astrocytes were slightly increased in the dentate gyrus of hippocampus in the knockout group, although we could not find any statistical significance between wild and knockout groups. During adult neurogenesis, neural stem cells are determined to choose either neuronal or glial cell fate, but the list of participated genes and the mechanism are not clearly defined (Hodge et al 2012;Klempin et al 2012;Ro et al 2013). Among those genes, Hes6 is known to participate in neuronal differentiation and also repressed the differentiation into astrocytes in cell culture (Jhas et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Hairy and Enhancer of Split 6 (Hes6) Deficiency in Mouse Impairs Neuroblast Differentiation in Dentate Gyrus Without Affecting Cell Proliferation and Integration into Mature Neurons

Nam

Kim

et al. 2015

Cell Mol Neurobiol

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Hes6 is a member of the hairy-enhancer of split homolog (Hes) family of transcription factors and interacts with other Hes family genes. During development, Hes genes are expressed in neural stem cells and progenitor cells. However, the role of Hes6 in adult hippocampal neurogenesis remains unclear. We therefore investigated the effects of Hes6 on adult hippocampal neurogenesis, by comparing Hes6 knockout and wild-type mice. To this end, we immunostained for markers of neural stem cells and progenitor cells (nestin), proliferating cells (Ki67), post-mitotic neuroblasts and immature neurons (doublecortin, DCX), mature neuronal cells (NeuN), and astrocyte (S100β). We also injected 5-bromo-2'-deoxyuridine (BrdU) to trace the fate of mitotic cells. Nestin- and Ki67-positive proliferating cells did now show any significant differences between wild and knockout groups. Hes6 knockout negatively affects neuroblast differentiation based on DCX immunohistochemistry. On the contrary, the ratio of the BrdU and NeuN double-positive cells did not show any significance, even though it was slightly higher in the knockout group. These results suggest that Hes6 is involved in the regulation of neuroblast differentiation during adult neurogenesis, but does not influence integration into mature neurons.

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“…This conserved mechanism was not relevant to longevity in C. elegans but, alternatively, may be involved in other FOXO functions, particularly functions such as stem cell maintenance in mammals (45,46). If so, in view of the notion that aberrant stem cell function is a hallmark of aging (47), our findings will provide new insights into the molecular mechanisms of aging and the pathogenesis of age-related diseases, including type 2 diabetes, Alzheimer's disease, and cancer.…”

Section: Discussionmentioning

confidence: 99%

Nontranscriptional Function of FOXO1/DAF-16 Contributes to Translesion DNA Synthesis

Daitoku

Kaneko

Yoshimochi

et al. 2016

Molecular and Cellular Biology

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Forkhead box O (FOXO; DAF-16 in nematodes) transcription factors activate a program of genes that control stress resistance, metabolism, and life span. Given the adverse impact of the stochastic DNA damage on organismal development and aging, we examined the role of FOXO/DAF-16 in UV-induced DNA damage response. Knockdown of FOXO1 but not of FOXO3a increases sensitivity to UV irradiation when exposed during S phase, suggesting a contribution of FOXO1 to translesion DNA synthesis (TLS), a replicative bypass of UV-induced DNA lesions. Actually, FOXO1 depletion results in sustained activation of ATR-Chk1 signaling and a reduction of proliferating cell nuclear antigen (PCNA) monoubiquitination following UV irradiation. FOXO1 does not alter the expression of TLS-related genes, but it binds to replication protein A 1 (RPA1), which coats single-stranded DNA and acts as a scaffold for TLS. In Caenorhabditis elegans, daf-16-null mutants show UV-induced retardation in larval development and are rescued by overexpressing a DAF-16 mutant lacking the transactivation domain but not a mutant whose amino acid substitutions render it unable to interact with RPA1. Thus, our findings demonstrate that FOXO1/DAF-16 is a functional component in TLS independent of its transactivation activity.

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FoxOs in neural stem cell fate decision

Cited by 28 publications

References 191 publications

FoxO6 affects Plxna4-mediated neuronal migration during mouse cortical development

FoxO6 affects Plxna4-mediated neuronal migration during mouse cortical development

Hairy and Enhancer of Split 6 (Hes6) Deficiency in Mouse Impairs Neuroblast Differentiation in Dentate Gyrus Without Affecting Cell Proliferation and Integration into Mature Neurons

Nontranscriptional Function of FOXO1/DAF-16 Contributes to Translesion DNA Synthesis

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