神经元非常长寿,必须保持其功能特征的非分裂细胞(例如,电性能,化学信号)用于延长的时间-在人类中几十年。神经元如何完成这一令人难以置信的壮举还知之甚少。这里,我们回顾了最近的进展,主要在线虫C.线虫中,增强了我们对使有丝分裂后神经元在不同生命阶段维持其功能的分子机制的理解。我们从“末端选择器”开始-建立和维持神经元身份所必需的转录因子。我们重点介绍了五个终端选择器的新发现(CHE-1[玻璃],UNC-3[Collier/Ebf1-4],LIN-39[Scr/Dfd/Hox4-5],UNC-86[Acj6/Brn3a-c],来自不同转录因子家族的AST-1[Etv1/ER81])(ZNF,COE,HOX,POU,ETS)。我们比较了这些因子在C.elegans的特定神经元类型中的功能及其在其他无脊椎动物中的直系同源物的作用(D.黑腹)和脊椎动物(M.musculus)系统,突出显著的功能保护。最后,我们反思最近的发现涉及染色质修饰蛋白,如组蛋白甲基转移酶和Polycomb蛋白,在神经元末端身份的控制中。总之,这些关于转录因子和染色质修饰剂的新研究不仅揭示了神经元身份维持的基本问题,但也概述了可能在其他长寿命中运作的基因调控机制原理,有丝分裂后的细胞类型。
Neurons are remarkably long-lived, non-dividing cells that must maintain their functional features (e.g., electrical properties, chemical signaling) for extended periods of time - decades in humans. How neurons accomplish this incredible feat is poorly understood. Here, we review recent advances, primarily in the nematode C. elegans, that have enhanced our understanding of the molecular mechanisms that enable post-mitotic neurons to maintain their functionality across different life stages. We begin with \"terminal selectors\" - transcription factors necessary for the establishment and maintenance of neuronal identity. We highlight new findings on five terminal selectors (CHE-1 [Glass], UNC-3 [Collier/Ebf1-4], LIN-39 [Scr/Dfd/Hox4-5], UNC-86 [Acj6/Brn3a-c], AST-1 [Etv1/ER81]) from different transcription factor families (ZNF, COE, HOX, POU, ETS). We compare the functions of these factors in specific neuron types of C. elegans with the actions of their orthologs in other invertebrate (D. melanogaster) and vertebrate (M. musculus) systems, highlighting remarkable functional conservation. Finally, we reflect on recent findings implicating chromatin-modifying proteins, such as histone methyltransferases and Polycomb proteins, in the control of neuronal terminal identity. Altogether, these new studies on transcription factors and chromatin modifiers not only shed light on the fundamental problem of neuronal identity maintenance, but also outline mechanistic principles of gene regulation that may operate in other long-lived, post-mitotic cell types.