Genetic ablation of <i>Rest</i> leads to in vitro-specific derepression of neuronal genes during neurogenesis

Aoki, Hitomi; Hara, Akira; Era, Takumi; Kunisada, Takahiro; Yamada, Yasuhiro

doi:10.1242/dev.072272

Cited by 54 publications

(94 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While this manuscript was in preparation, a report was published showing that a neural-specific conditional Rest knockout does not alter neurogenesis, although effects were noted in cultured cells isolated from mouse (Aoki et al, 2012). Although further analysis of rest conditional knockouts is required, these findings support our conclusion that Rest is not essential for neurogenesis and highlight similarities between Rest function in zebrafish and mice.…”

Section: Figuresupporting

confidence: 71%

Zebrafish rest regulates developmental gene expression but not neurogenesis

et al. 2012

View full text Add to dashboard Cite

SUMMARYThe transcriptional repressor Rest (Nrsf) recruits chromatin-modifying complexes to RE1 'silencer elements', which are associated with hundreds of neural genes. However, the requirement for Rest-mediated transcriptional regulation of embryonic development and cell fate is poorly understood. Conflicting views of the role of Rest in controlling cell fate have emerged from recent studies. To address these controversies, we examined the developmental requirement for Rest in zebrafish using zinc-finger nucleasemediated gene targeting. We discovered that germ layer specification progresses normally in rest mutants despite derepression of target genes during embryogenesis. This analysis provides the first evidence that maternal rest is essential for repression of target genes during blastula stages. Surprisingly, neurogenesis proceeds largely normally in rest mutants, although abnormalities are observed within the nervous system, including defects in oligodendrocyte precursor cell development and a partial loss of facial branchiomotor neuron migration. Mutants progress normally through embryogenesis but many die as larvae (after 12 days). However, some homozygotes reach adulthood and are viable. We utilized an RE1/NRSE transgenic reporter system to dynamically monitor Rest activity. This analysis revealed that Rest is required to repress gene expression in mesodermal derivatives including muscle and notochord, as well as within the nervous system. Finally, we demonstrated that Rest is required for long-term repression of target genes in non-neural tissues in adult zebrafish. Our results point to a broad role for Rest in fine-tuning neural gene expression, rather than as a widespread regulator of neurogenesis or cell fate.

show abstract

Section: Figuresupporting

confidence: 71%

Zebrafish rest regulates developmental gene expression but not neurogenesis

et al. 2012

View full text Add to dashboard Cite

show abstract

“…In the nucleus of embryonic and neural stem cells, the REST-CoREST complex is thought to restrict the precocious expression of genes that promote differentiation as well as assist in lineage differentiation. In particular, in embryonic and neural stem cells, as well as in nonneural cells that have already differentiated, REST-CoREST appears to be crucial to suppressing the neural gene program (Abrajano et al, 2009a;Aoki et al, 2012;Chen et al, 1998;Gao et al, 2011;Jørgensen et al, 2009b;Sun et al, 2005). Less is known about the upstream mechanisms regulating REST-CoREST itself.…”

Section: Discussionmentioning

confidence: 99%

“…Recognizing controversies in the literature, principally with respect to the role of REST in maintaining ESC pluripotency (Buckley et al, 2009;Jørgensen et al, 2009a;Jørgensen and Fisher, 2010;Singh et al, 2008;Yamada et al, 2010), REST has been proposed to modulate the balance of stemness versus differentiation and lineage specification of both embryonic and neural stem cells (Aoki et al, 2012;Gao et al, 2011;Su et al, 2004;Sun et al, 2005). These activities involve the direct repression (or in some cases activation) of differentiation-promoting genes, especially of the neural lineage.…”

Section: P120-catenin In Modulating Stemness and Differentiationmentioning

confidence: 99%

“…Core transcriptional regulators required for mouse and human embryonic stem cell (ESC) maintenance include Oct4 (also known as POU5F1), Sox2 and Nanog (Young, 2011). Repressor complexes, such as that organized about REST, likewise regulate embryonic and neural stem cells and their derivatives (Aoki et al, 2012;Gao et al, 2011;Sun et al, 2008;Sun et al, 2005). Whereas debate surrounds the role of REST in maintaining ESC self-renewal (Buckley et al, 2009;Jørgensen et al, 2009a;Jørgensen and Fisher, 2010;Singh et al, 2008), it is agreed that it participates in the self-renewal of neural stem cells (NSCs) (Gao et al, 2011), as well as differentiation from ESCs and NSCs, such as that towards neural lineages (Aoki et al, 2012;Chen et al, 1998;Yamada et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

P120-catenin regulates REST/CoREST, and modulates mouse embryonic stem cell differentiation

Lee

Furuta

et al. 2014

Journal of Cell Science

View full text Add to dashboard Cite

Although the canonical Wnt pathway and b-catenin have been extensively studied, less is known about the role of p120-catenin (also known as d1-catenin) in the nuclear compartment. Here, we report that p120-catenin binds and negatively regulates REST and CoREST (also known as Rcor1), a repressive transcriptional complex that has diverse developmental and pathological roles. Using mouse embryonic stem cells (mESCs), mammalian cell lines, Xenopus embryos and in vitro systems, we find that p120-catenin directly binds the REST-CoREST complex, displacing it from established gene targets to permit their transcriptional activation. Importantly, p120-catenin levels further modulate the mRNA and protein levels of Oct4 (also known as POU5F1), Nanog and Sox2, and have an impact upon the differentiation of mESCs towards neural fates. In assessing potential upstream inputs to this new p120-catenin-REST-CoREST pathway, REST gene targets were found to respond to the level of E-cadherin, with evidence suggesting that p120-catenin transduces signals between Ecadherin and the nucleus. In summary, we provide the first evidence for a direct upstream modulator and/or pathway regulating REST-CoREST, and reveal a substantial role for p120-catenin in the modulation of stem cell differentiation.

show abstract

“…The forkhead domain transcription factor FoxO3 is expressed in Sox2 + NSCs, and the absence of FoxO3 leads to a failure of NSCs to return to the quiescent state, ultimately leading to the depletion of the NSC pool (Renault et al 2009). In addition, the RE1 silencing transcription factor (REST), also known as NRSF, functions to repress the neuronal differentiation program in embryonic stem (ES) cells and early embryonic development (Yamada et al 2010;Mandel et al 2011;Aoki et al 2012;Soldati et al 2012). Recent work from my laboratory found that REST is expressed in type 1 cells, but is down-regulated in a subset of Ascl1 + cells and the majority of NeuroD1 + cells (Gao et al 2011).…”

Section: Maintenance and Cell Fate Specification Of Sgz Nscsmentioning

confidence: 99%

Orchestrating transcriptional control of adult neurogenesis

Hsieh¹

2012

Genes Dev.

186

166

View full text Add to dashboard Cite

Stem cells have captured our imagination and generated hope, representing a source of replacement cells to treat a host of medical conditions. Tucked away in specialized niches, stem cells maintain tissue function and rejuvenate organs. Balancing the equation between cellular supply and demand is especially important in the adult brain, as neural stem cells (NSCs) in two discrete regions, the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ) next to the lateral ventricles, continuously self-renew and differentiate into neurons in a process called adult neurogenesis. Through the interplay of intrinsic and extrinsic factors, adult neurogenic niches ensure neuronal turnover throughout life, contributing to plasticity and homeostatic processes in the brain. This review summarizes recent progress on the molecular control of adult neurogenesis in the SGZ and SVZ, focusing on the role of specific transcription factors that mediate the progression from NSCs to lineagecommitted progenitors and, ultimately, the generation of mature neurons and glia.

show abstract

Genetic ablation of Rest leads to in vitro-specific derepression of neuronal genes during neurogenesis

Cited by 54 publications

References 42 publications

Zebrafish rest regulates developmental gene expression but not neurogenesis

Zebrafish rest regulates developmental gene expression but not neurogenesis

P120-catenin regulates REST/CoREST, and modulates mouse embryonic stem cell differentiation

Orchestrating transcriptional control of adult neurogenesis

Contact Info

Product

Resources

About