Yang Marty G, West Anne E
Department of Neurobiology, Duke University, Durham, NC.
Yale J Biol Med. 2016 Dec 23;89(4):457-470. eCollection 2016 Dec.
The dynamic orchestration of gene expression is crucial for the proper differentiation, function, and adaptation of cells. In the brain, transcriptional regulation underlies the incredible diversity of neuronal cell types and contributes to the ability of neurons to adapt their function to the environment. Recently, novel methods for genome and epigenome editing have begun to revolutionize our understanding of gene regulatory mechanisms. In particular, the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has proven to be a particularly accessible and adaptable technique for genome engineering. Here, we review the use of CRISPR/Cas9 in neurobiology and discuss how these studies have advanced understanding of nervous system development and plasticity. We cover four especially salient applications of CRISPR/Cas9: testing the consequences of enhancer mutations, tagging genes and gene products for visualization in live cells, directly activating or repressing enhancers , and manipulating the epigenome. In each case, we summarize findings from recent studies and discuss evolving adaptations of the method.
基因表达的动态调控对于细胞的正常分化、功能及适应性至关重要。在大脑中，转录调控是神经元细胞类型惊人多样性的基础，并有助于神经元使其功能适应环境的能力。最近，基因组和表观基因组编辑的新方法已开始彻底改变我们对基因调控机制的理解。特别是，成簇规律间隔短回文重复序列（CRISPR）/Cas9系统已被证明是一种特别易于使用且适应性强的基因组工程技术。在此，我们综述CRISPR/Cas9在神经生物学中的应用，并讨论这些研究如何推动了对神经系统发育和可塑性的理解。我们涵盖了CRISPR/Cas9的四个特别突出的应用：测试增强子突变的后果、标记基因和基因产物以便在活细胞中可视化、直接激活或抑制增强子以及操纵表观基因组。在每种情况下，我们总结近期研究的发现并讨论该方法不断发展的适应性。
