Let-7-complex microRNAs regulate the temporal identity of Drosophila mushroom body neurons via chinmo.

Let-7-complex microRNAs regulate the temporal identity of Drosophila mushroom body neurons via chinmo.
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DOI:
10.1016/j.devcel.2012.05.013
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发表时间:
2012-07-17
期刊:
影响因子:
11.8
通讯作者:
Sokol, Nicholas S.
Sokol, Nicholas S.
中科院分区:
生物学1区
文献类型:
--
作者:
Wu, Yen-Chi;Chen, Ching-Huan;Mercer, Adam;Sokol, Nicholas S.

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许多神经谱系显示出一种时间模式,但控制神经元亚型有序产生的机制尚不清楚。本研究表明,在蘑菇体(MB)谱系中,从let-7复合物(let-7- c)位点共转录的果蝇let-7和miR-125调节转录因子chinmo来控制时间细胞的命运。我们发现,当三种MB亚型发生转变时,let-7-C在有丝分裂后的神经元中被激活。let-7-C的缺失或增加分别延迟或加速这些转变,并导致细胞命运的转变。与我们在最近发现的chinmo 3'UTR的约6kb延伸中发现的let-7和miR-125位点一致,chinmo在let-7- c突变型mb中升高。此外,我们发现let-7-C作用于chinmo上游,而let-7-C表型是由chinmo升高引起的。因此,这些最初在秀丽隐杆线虫中发现的异慢性mirna,在不同双边体发育过程中奠定了祖细胞多能性的基础。
Many neural lineages display a temporal pattern, but the mechanisms controlling the ordered production of neuronal subtypes remains unclear. Here, we show that Drosophila let-7 and miR-125, co-transcribed from the let-7-Complex (let-7-C) locus, regulate the transcription factor chinmo to control temporal cell fate in the mushroom body (MB) lineage. We find that let-7-C is activated in post-mitotic neurons born during the larval-to-pupal transition, when transitions between three MB subtypes occur. Loss or increase of let-7-C delays or accelerates these transitions, respectively, and lead to cell fate transformations. Consistent with our identification of let-7 and miR-125 sites in a recently identified ~6kb extension of the chinmo 3‘UTR, Chinmo is elevated in let-7-C mutant MBs. In addition, we show that let-7-C acts upstream of chinmo and let-7-C phenotypes are caused by elevated chinmo. Thus, these heterochronic miRNAs, originally identified in C. elegans, underlie progenitor cell multipotency during the development of diverse bilateria.
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