Max Planck Research Group of Gene Expression and Signaling, Max Planck Institute for Biophysical Chemistry, Goettingen, Germany.
EMBO J. 2012 Dec 12;31(24):4511-23. doi: 10.1038/emboj.2012.298. Epub 2012 Nov 16.
Mammalian neuronal stem cells produce multiple neuron types in the course of an individual's development. Similarly, neuronal progenitors in the Drosophila brain generate different types of closely related neurons that are born at specific time points during development. We found that in the post-embryonic Drosophila brain, steroid hormones act as temporal cues that specify the cell fate of mushroom body (MB) neuroblast progeny. Chronological regulation of neurogenesis is subsequently mediated by the microRNA (miRNA) let-7, absence of which causes learning impairment due to morphological MB defects. The miRNA let-7 is required to regulate the timing of α'/β' to α/β neuronal identity transition by targeting the transcription factor Abrupt. At a cellular level, the ecdysone-let-7-Ab signalling pathway controls the expression levels of the cell adhesion molecule Fasciclin II in developing neurons that ultimately influences their differentiation. Our data propose a novel role for miRNAs as transducers between chronologically regulated developmental signalling and physical cell adhesion.
哺乳动物神经元干细胞在个体发育过程中产生多种神经元类型。同样,果蝇大脑中的神经元祖细胞也产生不同类型的密切相关的神经元,这些神经元在发育过程中的特定时间点产生。我们发现,在胚胎后果蝇大脑中,类固醇激素作为时间线索,指定蘑菇体(MB)神经母细胞后代的细胞命运。神经发生的时间调控随后由 microRNA(miRNA)let-7 介导,其缺失会导致由于 MB 形态缺陷而导致学习障碍。miRNA let-7 通过靶向转录因子 Abrupt 来调节 α'/β' 到 α/β 神经元身份转变的时间。在细胞水平上,蜕皮激素-let-7-Ab 信号通路控制发育神经元中细胞粘附分子 Fasciclin II 的表达水平,最终影响其分化。我们的数据提出了 miRNAs 作为时间调节发育信号和物理细胞粘附之间的转换器的新作用。