Valproic acid, a histone deacetylase inhibitor, regulates cell proliferation in the adult zebrafish optic tectum

Dozawa, Miki; Kono, Hiromitsu; Sato, Yuki; Itō, Yoko; Tanaka, Hideomi; Ohshima, Toshio

doi:10.1002/dvdy.24173

Cited by 34 publications

(26 citation statements)

References 47 publications

(78 reference statements)

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“…However, the molecular mechanisms underlying NSC proliferation and differentiation are largely unknown. We have shown that Notch signaling regulates NSC proliferation (Dozawa et al, 2014); we also observed the gene expression of other signalingrelated molecules known to be involved in NSC proliferation and differentiation.…”

Section: Introductionmentioning

confidence: 70%

Wnt and Shh signals regulate neural stem cell proliferation and differentiation in the optic tectum of adult zebrafish

Shitasako

Itō

Ito

et al. 2017

Developmental Neurobiology

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Adult neurogenesis occurs more commonly in teleosts, represented by zebrafish, than in mammals. Zebrafish is therefore considered a suitable model to study adult neurogenesis, for which the regulatory molecular mechanisms remain little known. Our previous study revealed that neuroepithelial‐like neural stem cells (NSCs) are located at the edge of the dorsomedial region. We also showed that Notch signaling inhibits NSC proliferation in this region. In the present study, we reported the expression of Wnt and Shh signaling components in this region of the optic tectum. Moreover, inhibitors of Wnt and Shh signaling suppressed NSC proliferation, suggesting that these pathways promote NSC proliferation. Shh is particularly required for maintaining Sox2‐positive NSCs. Our experimental data also indicate the involvement of these signaling pathways in neural differentiation from NSCs. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1206–1220, 2017

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Section: Introductionmentioning

confidence: 70%

Wnt and Shh signals regulate neural stem cell proliferation and differentiation in the optic tectum of adult zebrafish

Shitasako

Itō

Ito

et al. 2017

Developmental Neurobiology

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“…It has been well established that HDAC inhibitors decrease the proliferation of NSCs (Dozawa et al., 2014). We further determined whether the mTOR pathway mediated the effect of VPA on the proliferation of NSCs.…”

Section: Resultsmentioning

confidence: 99%

PI3K/AKT/mTOR Signaling Mediates Valproic Acid-Induced Neuronal Differentiation of Neural Stem Cells through Epigenetic Modifications

Zhang

et al. 2017

Stem Cell Reports

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SummaryAlthough valproic acid (VPA), has been shown to induce neuronal differentiation of neural stem cells (NSCs), the underlying mechanisms remain poorly understood. Here we investigated if and how mammalian target of rapamycin (mTOR) signaling is involved in the neuronal differentiation of VPA-induced NSCs. Our data demonstrated that mTOR activation not only promoted but also was necessary for the neuronal differentiation of NSCs induced by VPA. We further found that inhibition of mTOR signaling blocked demethylation of neuron-specific gene neurogenin 1 (Ngn1) regulatory element in induced cells. These are correlated with the significant alterations of passive DNA demethylation and the active DNA demethylation pathway in the Ngn1 promoter, but not the suppression of lysine-specific histone methylation and acetylation in the promoter region of Ngn1. These findings highlight a potentially important role for mTOR signaling, by working together with DNA demethylation, to influence the fate of NSCs via regulating the expression of Ngn1 in VPA-induced neuronal differentiation of NSCs.

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“…Notch signaling has also been reported to regulate RG proliferation after stab injury in the telencephalon (Kishimoto, Shimizu, & Sawamoto, 2012). In the optic tectum, Notch signaling related genes such as notch and delta family genes and bHLH transcriptional factors her4 and her6 are expressed, and Notch signaling regulates the proliferation of NE (Chapouton et al, 2011;de Oliveira-Carlos, Ganz, Hans, Kaslin, & Brand, 2013;Dozawa et al, 2014). We analyzed the expression levels of her4 and her6 in the optic tectum after stab injury and analyzed the effects of Notch inhibition on RG proliferation and differentiation into neurons after stab injury.…”

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confidence: 99%

Involvement of sonic hedgehog and notch signaling in regenerative neurogenesis in adult zebrafish optic tectum after stab injury

Ueda

Shimizu

et al. 2018

J of Comparative Neurology

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Unlike humans and other mammals, adult zebrafish have the superior capability to recover from central nervous system (CNS) injury. We previously found that proliferation of radial glia (RG) is induced in response to stab injury in optic tectum and that new neurons are generated from RG after stab injury. However, molecular mechanisms which regulate proliferation and differentiation of RG are not well known. In the present study, we investigated Shh and Notch signaling as potential mechanisms regulating regeneration in the optic tectum of adult zebrafish. We used Shh reporter fish and confirmed that canonical Shh signaling is activated specifically in RG after stab injury. Moreover, we have shown that Shh signaling promotes RG proliferation and suppresses their differentiation into neurons after stab injury. In contrast, Notch signaling was down-regulated after stab injury, indicated by the decrease in the expression level of her4 and her6, a target gene of Notch signaling. We also found that inhibition of Notch signaling after stab injury induced more proliferative RG, but that inhibition of Notch signaling inhibited generation of newborn neurons from RG after stab injury. These results suggest that high level of Notch signaling keeps RG quiescent and that appropriate level of Notch signaling is required for generation of newborn neurons from RG. Under physiological condition, activation of Shh signaling or inhibition of Notch signaling also induced RG proliferation. In adult optic tectum of zebrafish, canonical Shh signaling and Notch signaling play important roles in proliferation and differentiation of RG in physiological and regenerative conditions.

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Valproic acid, a histone deacetylase inhibitor, regulates cell proliferation in the adult zebrafish optic tectum

Cited by 34 publications

References 47 publications

Wnt and Shh signals regulate neural stem cell proliferation and differentiation in the optic tectum of adult zebrafish

Wnt and Shh signals regulate neural stem cell proliferation and differentiation in the optic tectum of adult zebrafish

PI3K/AKT/mTOR Signaling Mediates Valproic Acid-Induced Neuronal Differentiation of Neural Stem Cells through Epigenetic Modifications

Involvement of sonic hedgehog and notch signaling in regenerative neurogenesis in adult zebrafish optic tectum after stab injury

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