Regulation of proliferation and histone acetylation in embryonic neural precursors by CREB/CREM signaling.

Neurogenesis (Austin, Tex.) Pub Date : 2014-11-26 eCollection Date: 2014-01-01 DOI:10.4161/23262125.2014.970883
Rosanna Parlato, Claudia Mandl, Gabriele Hölzl-Wenig, Birgit Liss, Kerry L Tucker, Francesca Ciccolini
{"title":"Regulation of proliferation and histone acetylation in embryonic neural precursors by CREB/CREM signaling.","authors":"Rosanna Parlato,&nbsp;Claudia Mandl,&nbsp;Gabriele Hölzl-Wenig,&nbsp;Birgit Liss,&nbsp;Kerry L Tucker,&nbsp;Francesca Ciccolini","doi":"10.4161/23262125.2014.970883","DOIUrl":null,"url":null,"abstract":"<p><p>The transcription factor CREB (cAMP-response element binding protein) regulates differentiation, migration, survival and activity-dependent gene expression in the developing and mature nervous system. However, its specific role in the proliferation of embryonic neural progenitors is still not completely understood. Here we investigated how CREB regulates proliferation of mouse embryonic neural progenitors by a conditional mutant lacking Creb gene in neural progenitors. In parallel, we explored possible compensatory effects by the genetic ablation of another member of the same gene family, the cAMP-responsive element modulator (Crem). We show that CREB loss differentially impaired the proliferation, clonogenic potential and self-renewal of precursors derived from the ganglionic eminence (GE), in comparison to those derived from the cortex. This phenotype was associated with a specific reduction of histone acetylation in the GE of CREB mutant mice, and this reduction was rescued in vivo by inhibition of histone deacetylation. These observations indicate that the impaired proliferation could be caused by a reduced acetyltransferase activity in Creb conditional knock-out mice. These findings support a crucial role of CREB in controlling embryonic neurogenesis and propose a novel mechanism by which CREB regulates embryonic neural development. </p>","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2014-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/23262125.2014.970883","citationCount":"3","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurogenesis (Austin, Tex.)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4161/23262125.2014.970883","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2014/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 3

Abstract

The transcription factor CREB (cAMP-response element binding protein) regulates differentiation, migration, survival and activity-dependent gene expression in the developing and mature nervous system. However, its specific role in the proliferation of embryonic neural progenitors is still not completely understood. Here we investigated how CREB regulates proliferation of mouse embryonic neural progenitors by a conditional mutant lacking Creb gene in neural progenitors. In parallel, we explored possible compensatory effects by the genetic ablation of another member of the same gene family, the cAMP-responsive element modulator (Crem). We show that CREB loss differentially impaired the proliferation, clonogenic potential and self-renewal of precursors derived from the ganglionic eminence (GE), in comparison to those derived from the cortex. This phenotype was associated with a specific reduction of histone acetylation in the GE of CREB mutant mice, and this reduction was rescued in vivo by inhibition of histone deacetylation. These observations indicate that the impaired proliferation could be caused by a reduced acetyltransferase activity in Creb conditional knock-out mice. These findings support a crucial role of CREB in controlling embryonic neurogenesis and propose a novel mechanism by which CREB regulates embryonic neural development.

Abstract Image

Abstract Image

Abstract Image

CREB/CREM信号对胚胎神经前体增殖和组蛋白乙酰化的调控。
转录因子CREB (camp反应元件结合蛋白)调节发育和成熟神经系统的分化、迁移、存活和活性依赖基因表达。然而,其在胚胎神经祖细胞增殖中的具体作用尚不完全清楚。在这里,我们研究了CREB如何通过神经祖细胞中缺乏CREB基因的条件突变体调节小鼠胚胎神经祖细胞的增殖。与此同时,我们探索了同一基因家族的另一个成员cAMP-responsive element modulator (Crem)的基因消融可能产生的补偿效应。我们发现,与来自皮质的前体相比,CREB的缺失对神经节隆起(GE)的前体的增殖、克隆潜能和自我更新的损害有所不同。这种表型与CREB突变小鼠GE中组蛋白乙酰化的特异性减少有关,并且这种减少在体内通过抑制组蛋白去乙酰化来恢复。这些观察结果表明,Creb条件敲除小鼠的增殖受损可能是由乙酰转移酶活性降低引起的。这些发现支持了CREB在控制胚胎神经发生中的关键作用,并提出了CREB调节胚胎神经发育的新机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信