Functional regulation of FoxO1 in neural stem cell differentiation

Kim, D. Y.; Hwang, Inah; Muller, Florian L.; Paik, Jihye

doi:10.1038/cdd.2015.123

Cited by 80 publications

(79 citation statements)

References 49 publications

(47 reference statements)

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“…In normal neural progenitors, FOXO3 inhibits ASCL1-dependent neurogenesis and also restrains neurogenesis in vivo (Webb et al, 2013). Similarly, constitutively active FOXO1 inhibits while its knockdown increases neurogenic differentiation of neural progenitors (Kim, Hwang, Muller & Paik, 2015). These findings together raise the possibility that FOXOs suppress lineage commitment and such activity may help maintaining the NSC reserves throughout the lifetime.…”

Section: Neural Development and Stem Cell Maintenancementioning

confidence: 99%

FOXO in Neural Cells and Diseases of the Nervous System

Santo

Paik

2018

Current Topics in Developmental Biology

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The evolutionarily-conserved FOXO family of transcription factors has emerged as a significant arbiter of neural cell fate and function. From the neural stem cell state through mature neurons under both physiological and pathological conditions they have been found to modulate neural cell survival, stress responses, lineage commitment and neuronal signaling. Lineage-specific FOXO knockout mice have provided an invaluable tool for the dissection of FOXO biology in the nervous system. Within the neural stem cell compartments of the brain FOXOs are required for the maintenance of NSC quiescence and for the clearance of reactive oxygen species. Within mature neurons FOXO transcriptional activity is essential for the prevention of age-dependent axonal degeneration. Acutely, FOXO3 has been found to cause axonal degeneration upon withdrawal of neurotrophic factors. In more active neural signaling, FOXO6 promotes increased dendritic spine density of hippocampal neurons and is required for the consolidation of memories. In addition to the central nervous system (CNS) FOXOs also influence the functionality of the peripheral nervous system (PNS). FOXO1 knockout within the PNS results in a reduction of sympathetic tone and decreased levels of brain-derived norepinephrine and lower energy expenditure. FOXO3 knockout mice have impaired hearing which may be due to defects in synapse localization within the ear. Given the scope of FOXO activities in both the CNS and PNS it will be of interest to study FOXOs within the context of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s and Amyotrophic Lateral Sclerosis. From within the nervous system FOXOs may also regulate important parameters such as whole-body metabolism, motor function and catecholamine production; making FOXOs key players in physiologic homeostasis.

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Section: Neural Development and Stem Cell Maintenancementioning

confidence: 99%

FOXO in Neural Cells and Diseases of the Nervous System

Santo

Paik

2018

Current Topics in Developmental Biology

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“…One question that arises from our results is the precise genes that are regulated by miR-9. The transcription factor FOXO1 has been identified as a target of miR-9 in haematopoietic cells and neural cells [21,35]. We found that a miR-9 mimic significantly inhibited the activity of the 3′-untranslated region of Foxo1 mRNA and FOXO1 expression in mouse liver cells (data not shown).…”

Section: Discussionmentioning

confidence: 73%

“…The transcription factor FOXO1 is a regulator of gluconeogenesis and is a target of miR-9 in haematopoietic cells and neural cells [21,35]. We investigated whether FOXO1 is required for the miR-9 inhibition of gluconeogenesis and glucose output.…”

Section: Mir-9 Suppresses Gluconeogenesis and Hpg By Directly Targetimentioning

confidence: 99%

A decrease in hepatic microRNA-9 expression impairs gluconeogenesis by targeting FOXO1 in obese mice

Yan

Chen

et al. 2016

Diabetologia

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Aim/hypothesis MicroRNA-9 (miR-9) is involved in the regulation of pancreatic beta cell function. However, its role in gluconeogenesis is still unclear. Our objective was to investigate the role of miR-9 in hepatic glucose production (HGP). Methods MiR-9 expression was measured in livers of high-fat diet (HFD) mice and ob/ob mice. The methylation status of the miR-9-3 promoter regions in hepatocytes was determined by the methylation-specific PCR procedure. The binding activity of DNA methyltransferase (DNMT)1, DNMT3a and DNMT3b on the miR-9-3 promoter was detected by chromatin immunoprecipitation (ChIP) and quantitative real-time PCR assays. HGP was evaluated in vitro and in vivo. Glucose tolerance, insulin tolerance and pyruvate tolerance tests were also performed. Results Reduced miR-9 expression and hypermethylation of the miR-9-3 promoter were observed in the livers of obese mice. Further study showed that the binding of DNMT1, but not of DNMT3a and DNMT3b, to the miR-9-3 promoter was increased in hepatocytes from ob/ob mice. Knockdown of DNMT1 alleviated the decrease in hepatic miR-9 expression in vivo and in vitro. Overexpression of hepatic miR-9 improved insulin sensitivity in obese mice and inhibited HGP. In addition, deletion of hepatic miR-9 led to an increase in random and fasting blood glucose levels in lean mice. Importantly, silenced forkhead box O1 (FOXO1) expression reversed the gluconeogenesis and glucose production in hepatocytes induced by miR-9 deletion. Conclusions/interpretation Our observations suggest that the decrease in miR-9 expression contributes to an inappropriately activated gluconeogenesis in obese mice.

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“…The nucleotide sequence of miR‐9 is 100% identical from insects to mammals, suggesting that its functional preservation is evolutionarily important. In mammals, miR‐9 is highly expressed in neurogenic areas, and its expression is gradually increased during neuronal differentiation . Consistent with this expression pattern, miR‐9 accelerates neural differentiation at the expense of NSPC proliferation inhibition.…”

Section: Post‐transcriptional Regulatorsmentioning

confidence: 66%

“…Id2, which antagonizes neuronal differentiation, is also suppressed by miR‐9 . Recently, FoxO1 was determined to be a new molecular target of miR‐9 . Since FoxO1 cooperates with the Notch pathway to NSPC maintenance, the reduced expression of FoxO1 by miR‐9 induced cell differentiation.…”

Section: Post‐transcriptional Regulatorsmentioning

confidence: 99%

Post‐transcriptional regulation of gene expression in neural stem cells

Kim

2016

Cell Biochemistry & Function

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Expression of each gene can be controlled at several steps during the flow of genetic information from DNA to protein. Tight regulation of gene expression is especially important for stem cells because of their greater ripple effects, compared with terminally differentiated cells. Dysregulation of gene expression arising in stem cells can be perpetuated within the stem cell pool via self-renewal throughout life. In addition, transcript profiles within stem cells can determine the selective advantage or disadvantage of each cell, leading to changes in cell fate, such as a tendency for proliferation, death, and differentiation. The identification of neural stem/progenitor cells (NSPCs) and greater understanding of their cellular physiology have raised the possibility of using NSPCs to replace damaged or injured neurons. However, an accurate grasp of gene expression control must take precedence in order to use NSPCs in therapies for neurological diseases. Recently, accumulating evidence has demonstrated the importance of post-transcriptional regulation in NSPC fate decisions. In this review, we will summarize and discuss the recent findings on key mRNA modulators and their vital roles in NSPC homeostasis. Copyright © 2016 John Wiley & Sons, Ltd.

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Functional regulation of FoxO1 in neural stem cell differentiation

Cited by 80 publications

References 49 publications

FOXO in Neural Cells and Diseases of the Nervous System

FOXO in Neural Cells and Diseases of the Nervous System

A decrease in hepatic microRNA-9 expression impairs gluconeogenesis by targeting FOXO1 in obese mice

Post‐transcriptional regulation of gene expression in neural stem cells

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