美国斯坦福大学Kang Shen团队近期取得重要工作进展，他们研究提出，活性调控的转录程序直接驱动突触发生。相关研究成果2024年8月5日在线发表于《自然—神经科学》杂志上。

据介绍，尽管突触的分子组成和结构已经得到了广泛的探索，但人们对哪些遗传程序直接激活突触基因表达以及它们是如何被调节的知之甚少。

使用秀丽隐杆线虫多巴胺能神经元，研究人员发现EGL-43/MECOM和FOS-1/FOS控制着一个活动依赖性突触发生程序。任一因子的缺失都会严重降低突触前蛋白的表达。这两种因子都直接与突触基因的启动子结合，并与CUT同源框转录因子一起激活转录。egl-43和fos-1相互促进彼此的表达，增加fos-1与egl-43位点的结合亲和力会导致突触前蛋白表达和突触功能的增加。EGL-43调节多种转录因子的表达，包括定义多巴胺能身份多个方面的活性调节因子和发育因子。

总之，这一研究描述了发育过程中活动调节突触形成的稳健遗传程序。

附：英文原文

Title: An activity-regulated transcriptional program directly drives synaptogenesis

Author: Yee, Callista, Xiao, Yutong, Chen, Hongwen, Reddy, Anay R., Xu, Bing, Medwig-Kinney, Taylor N., Zhang, Wan, Boyle, Alan P., Herbst, Wendy A., Xiang, Yang Kevin, Matus, David Q., Shen, Kang

Issue&Volume: 2024-08-05

Abstract: Although the molecular composition and architecture of synapses have been widely explored, much less is known about what genetic programs directly activate synaptic gene expression and how they are modulated. Here, using Caenorhabditis elegans dopaminergic neurons, we reveal that EGL-43/MECOM and FOS-1/FOS control an activity-dependent synaptogenesis program. Loss of either factor severely reduces presynaptic protein expression. Both factors bind directly to promoters of synaptic genes and act together with CUT homeobox transcription factors to activate transcription. egl-43 and fos-1 mutually promote each other’s expression, and increasing the binding affinity of FOS-1 to the egl-43 locus results in increased presynaptic protein expression and synaptic function. EGL-43 regulates the expression of multiple transcription factors, including activity-regulated factors and developmental factors that define multiple aspects of dopaminergic identity. Together, we describe a robust genetic program underlying activity-regulated synapse formation during development.

DOI: 10.1038/s41593-024-01728-x

Source: https://www.nature.com/articles/s41593-024-01728-x