Cyclin D2 in the basal process of neural progenitors is linked to non-equivalent cell fates

Cyclin D2 in the basal process of neural progenitors is linked to non-equivalent cell fates
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DOI:
10.1038/emboj.2012.43
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发表时间:
2012-04-18
期刊:
影响因子:
11.4
通讯作者:
Osumi, Noriko
Osumi, Noriko
中科院分区:
生物学1区
文献类型:
--
作者:
Tsunekawa, Yuji;Britto, Joanne M.;Osumi, Noriko

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不对称细胞分裂在皮质生成过程中发挥着不可或缺的作用,以产生新的神经元,同时维持顶端祖细胞的自我更新池。有利于不对称分裂的细胞和分子决定因素尚未完全了解。在这里,我们确定了一种通过 Cyclin D2 mRNA 在基础过程中的主动运输和局部翻译产生细胞不对称性的新机制。该过程由 mRNA 3' 非翻译区 (3'UTR) 中发现的独特顺式调节序列调节。 Cyclin D2 蛋白向具有基底突的基底定位子细胞的不均等遗传赋予了不对称分裂后顶端祖细胞的更新。相反,顶端子细胞中 Cyclin D2 的耗尽会导致终末神经元分化。我们证明 Cyclin D2 也在类似区域内发育中的人类皮质中表达,从而表明它作为命运决定因素的作用是古老且保守的。 EMBO 杂志 (2012) 31, 1879-1892。 doi:10.1038/emboj.2012.43;在线发表 2012 年 3 月 6 日 主题类别:细胞与组织结构;神经科学
Asymmetric cell division plays an indispensable role during corticogenesis for producing new neurons while maintaining a self-renewing pool of apical progenitors. The cellular and molecular determinants favouring asymmetric division are not completely understood. Here, we identify a novel mechanism for generating cellular asymmetry through the active transportation and local translation of Cyclin D2 mRNA in the basal process. This process is regulated by a unique cis-regulatory sequence found in the 3' untranslated region (3'UTR) of the mRNA. Unequal inheritance of Cyclin D2 protein to the basally positioned daughter cell with the basal process confers renewal of the apical progenitor after asymmetric division. Conversely, depletion of Cyclin D2 in the apically positioned daughter cell results in terminal neuronal differentiation. We demonstrate that Cyclin D2 is also expressed in the developing human cortex within similar domains, thus indicating that its role as a fate determinant is ancient and conserved. The EMBO Journal (2012) 31, 1879-1892. doi:10.1038/emboj.2012.43; Published online 6 March 2012 Subject Categories: cell & tissue architecture; neuroscience