Cross-regulation of Connexin43 and β-catenin influences differentiation of human neural progenitor cells.
Cross-regulation of Connexin43 and β-catenin influences differentiation of human neural progenitor cells.
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DOI：
10.1038/cddis.2013.546
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发表时间：
2014-01-23
影响因子：
9
通讯作者：
Caldwell MA
中科院分区：
文献类型：
--
作者：
Rinaldi F;Hartfield EM;Crompton LA;Badger JL;Glover CP;Kelly CM;Rosser AE;Uney JB;Caldwell MA
Connexin43 （Cx43）是最广泛和最丰富表达的间隙连接（GJ）蛋白，它与细胞周期进程的调节密切相关。最近也认识到Cx43在神经分化过程中细胞粘附和迁移中的新作用，这强调了Cx43在其作为GJ蛋白的作用之外参与不同的生理过程。在这项研究中，我们利用介导Cx43蛋白过表达或敲低的病毒载体，探讨了Cx43在人神经祖细胞（hNPCs）分化中的功能。结果表明，在缺乏这种蛋白的情况下，胎儿皮质衍生的hNPCs以神经胶质表型为代价向神经元表型分化。此外，Cx43的沉默不影响hNPC的增殖率和凋亡细胞的数量。当GJ细胞间通讯被药理学阻断时，神经元数量的增加并未重现，这表明Cx43影响hNPCs分化的作用与GJ无关。此外，Cx43敲低显著增加β-catenin信号传导，已被证明在胚胎神经发育过程中调节前神经元基因的转录。我们的研究结果进一步支持了Cx43蛋白本身在发育和神经发生过程中调节关键信号通路的假设，而不仅仅是作为GJ蛋白。
Connexin43 (Cx43) is the most widely and abundantly expressed gap junction (GJ) protein and it is strongly associated with the regulation of cell cycle progression. Emerging roles for Cx43 in cell adhesion and migration during neural differentiation have also been recently recognized, and this has emphasized the involvement of Cx43 in different physiological process beyond its role as a GJ protein. In this study, we explore the function of Cx43 in the differentiation of human neural progenitor cells (hNPCs) using viral vectors that mediate the overexpression or knockdown of the protein. Results showed that in the absence of this protein fetal cortex-derived hNPCs differentiated toward a neuronal phenotype at expenses of a glial phenotype. Furthermore, the silencing of Cx43 did not affect hNPC proliferation rate or numbers of apoptotic cells. The increase in the number of neurons was not recapitulated when GJ intercellular communications were pharmacologically blocked, and this suggested that Cx43 was influencing hNPCs differentiation with a GJ-independent effect. In addition, Cx43 knockdown significantly increased β-catenin signaling, which has been shown to regulate the transcription of pro-neuronal genes during embryonic neural development. Our results add further support to the hypothesis that Cx43 protein itself regulates key signaling pathways during development and neurogenesis beyond its role as GJ protein.
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DOI：
10.1158/1078-0432.ccr-08-3131
发表时间：
2009-04-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Avissar M;Christensen BC;Kelsey KT;Marsit CJ
通讯作者：
Marsit CJ
影响因子：
11.5
作者：
Brockstein, Bruce E.
通讯作者：
Brockstein, Bruce E.
影响因子：
158.5
作者：
Bonner, JA;Harari, PM;Ang, KK
通讯作者：
Ang, KK
影响因子：
3.5
作者：
Brunner, Thomas B.;Kunz-Schughart, Leoni A.;Baumann, Michael
通讯作者：
Baumann, Michael
DOI：
10.1056/nejmoa0912217
发表时间：
2010-07-01
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ang KK;Harris J;Wheeler R;Weber R;Rosenthal DI;Nguyen-Tân PF;Westra WH;Chung CH;Jordan RC;Lu C;Kim H;Axelrod R;Silverman CC;Redmond KP;Gillison ML
通讯作者：
Gillison ML