Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA.
Department of Neuroscience, BCM, Houston, TX 77030, USA.
Biomolecules. 2020 Jul 1;10(7):985. doi: 10.3390/biom10070985.
Since its discovery in , the Notch signaling pathway has been studied in numerous developmental contexts in diverse multicellular organisms. The role of Notch signaling in nervous system development has been extensively investigated by numerous scientists, partially because many of the core Notch signaling components were initially identified through their dramatic 'neurogenic' phenotype of developing fruit fly embryos. Components of the Notch signaling pathway continue to be expressed in mature neurons and glia cells, which is suggestive of a role in the post-developmental nervous system. The Notch pathway has been, so far, implicated in learning and memory, social behavior, addiction, and other complex behaviors using genetic model organisms including and mice. Additionally, Notch signaling has been shown to play a modulatory role in several neurodegenerative disease model animals and in mediating neural toxicity of several environmental factors. In this paper, we summarize the knowledge pertaining to the post-developmental roles of Notch signaling in the nervous system with a focus on discoveries made using the fruit fly as a model system as well as relevant studies in , mouse, rat, and cellular models. Since components of this pathway have been implicated in the pathogenesis of numerous psychiatric and neurodegenerative disorders in human, understanding the role of Notch signaling in the mature brain using model organisms will likely provide novel insights into the mechanisms underlying these diseases.
自 Notch 信号通路于 1980 年代被发现以来,众多的多细胞生物在许多发育背景下对其进行了研究。许多科学家广泛研究了 Notch 信号在神经系统发育中的作用,部分原因是许多 Notch 信号核心成分最初是通过其在发育中的果蝇胚胎中的显著“神经生成”表型而被鉴定出来的。Notch 信号通路的成分在成熟神经元和神经胶质细胞中持续表达,这表明其在发育后的神经系统中具有重要作用。迄今为止,通过包括果蝇和小鼠在内的遗传模式生物研究表明,Notch 途径参与学习和记忆、社交行为、成瘾和其他复杂行为。此外, Notch 信号在几种神经退行性疾病模型动物中表现出调节作用,并介导几种环境因素的神经毒性。在本文中,我们总结了 Notch 信号在神经系统中的发育后作用的相关知识,重点介绍了使用果蝇作为模型系统的发现,以及在 、小鼠、大鼠和细胞模型中的相关研究。由于该通路的成分与人类多种精神和神经退行性疾病的发病机制有关,因此使用模式生物研究 Notch 信号在成熟大脑中的作用可能为这些疾病的机制提供新的见解。