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

被引:86
作者
Tsunekawa, Yuji [1 ]
Britto, Joanne M. [2 ]
Takahashi, Masanori [1 ]
Polleux, Franck [3 ]
Tan, Seong-Seng [2 ]
Osumi, Noriko [1 ]
机构
[1] Tohoku Univ, Grad Sch Med, Div Dev Neurosci, United Core Ctr Adv Res & Translat Med, Sendai, Miyagi 9808575, Japan
[2] Univ Melbourne, Florey Neurosci Inst, Brain Dev & Regenerat Lab, Melbourne, Vic, Australia
[3] Scripps Res Inst, Dorris Neurosci Ctr, Dept Cell Biol, La Jolla, CA 92037 USA
基金
英国医学研究理事会; 日本科学技术振兴机构;
关键词
asymmetric cell division; corticogenesis; Cyclin D2; mRNA subcellular localization; neuronal differentiation; CULTURED MAMMALIAN EMBRYOS; NEUROEPITHELIAL CELLS; CORTICAL NEUROGENESIS; ASYMMETRIC DIVISION; STEM-CELLS; DEVELOPING NEOCORTEX; DEVELOPING BRAIN; CEREBRAL-CORTEX; NEURONS ARISE; RADIAL GLIA;
D O I
10.1038/emboj.2012.43
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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
引用
收藏
页码:1879 / 1892
页数:14
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