Howard Hughes Medical Institute and Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Curr Opin Cell Biol. 2013 Apr;25(2):215-21. doi: 10.1016/j.ceb.2012.12.007. Epub 2013 Jan 29.
Mammalian neural development has been traditionally studied in the context of evolutionarily conserved signaling pathways and neurogenic transcription factors. Recent studies suggest that microRNAs, a group of highly conserved noncoding regulatory small RNAs also play essential roles in neural development and neuronal function. A part of their action in the developing nervous system is to regulate subunit compositions of BAF complexes (ATP-dependent chromatin remodeling complexes), which appear to have dedicated functions during neural development. Intriguingly, ectopic expression of a set of brain-enriched microRNAs, miR-9/9* and miR-124 that promote the assembly of neuron-specific BAF complexes, converts the nonneuronal fate of human dermal fibroblasts towards postmitotic neurons, thereby revealing a previously unappreciated instructive role of these microRNAs. In addition to these global effects, accumulating evidence indicates that many microRNAs could also function locally, such as at the growth cone or at synapses modulating synaptic activity and neuronal connectivity. Here we discuss some of the recent findings about microRNAs' activity in regulating various developmental stages of neurons.
哺乳动物神经发育的传统研究集中在进化保守的信号通路和神经发生转录因子上。最近的研究表明,microRNAs 作为一组高度保守的非编码调控小 RNA,在神经发育和神经元功能中也发挥着重要作用。它们在发育中的神经系统中的部分作用是调节 BAF 复合物(ATP 依赖性染色质重塑复合物)的亚基组成,而 BAF 复合物在神经发育中似乎具有专门的功能。有趣的是,一组脑富集的 microRNAs(miR-9/9* 和 miR-124)的异位表达促进了神经元特异性 BAF 复合物的组装,将人真皮成纤维细胞的非神经元命运转化为有丝分裂后的神经元,从而揭示了这些 microRNAs 的先前未被认识到的指导作用。除了这些全局效应外,越来越多的证据表明,许多 microRNAs 也可以在局部发挥作用,例如在生长锥或突触处调节突触活动和神经元连接。在这里,我们讨论了一些关于 microRNAs 在调节神经元各个发育阶段的活性的最新发现。