Department of Dermatology, The Saarland University Hospital, Homburg, Germany.
Adv Exp Med Biol. 2020;1227:1-7. doi: 10.1007/978-3-030-36422-9_1.
Evolutionary conserved Notch signaling is of high importance for embryogenesis and adult tissues, representing one of the most fascinating pathways that regulate key cell fate decisions and other core processes. This chapter gives a short introduction to the first volume of the book entitled Notch Signaling in Embryology and Cancer, that is intended to provide both basic scientists and clinicians who seek today`s clearest understanding of the molecular mechanisms that mediate Notch signaling with an authoritative day-to-day source. On a first look, Notch signaling, that first developed in metazoans and that was first discovered in a fruit fly, seems fallaciously simple, with its key feature being a direct link between an extracellular signal and transcriptional output without the requirement of an extended chain of protein intermediaries as needed by the majority of other signaling pathways. However, on a second, closer look, this obvious simplicity hides remarkable complexity. Notch signaling, that relies on an extensive collection of mechanisms that it exerts alongside of its core transcriptional machinery, orchestrates and governs cellular development by inducing and regulating communication between adjacent cells. In general, a cell expressing the Notch receptor can be activated in trans by ligands on an adjacent cell leading to alteration of transcription and cellular fate. However, ligands also have the ability to inhibit Notch signaling and this can be accomplished when both receptor and ligands are co-expressed in cis on the same cell. The so called non-canonical Notch pathways further diversify the potential outputs of Notch, and allow it to coordinate regulation of many aspects of cell biology. Fortunately, the generation and investigation of knockout mice and other animal models have in recent years resulted in a huge volume of new scientific informations concerning Notch gene function, allowing to dissect the role of specific Notch components for human development and health, and showing promise in opening new avenues for prevention and therapy of a broad variety of independent diseases, including cancer, although this goal is still challenging.
进化上保守的 Notch 信号对于胚胎发生和成人组织非常重要，它是调节关键细胞命运决定和其他核心过程的最迷人途径之一。本章简要介绍了题为《胚胎发生和癌症中的 Notch 信号》一书的第一卷，旨在为寻求当今对介导 Notch 信号的分子机制最清晰理解的基础科学家和临床医生提供权威的日常资源。乍一看，Notch 信号首先在后生动物中发展，并首先在果蝇中发现，它似乎是简单的，其关键特征是细胞外信号和转录输出之间的直接联系，而不需要像大多数其他信号途径那样需要延伸的蛋白质中间物链。然而，在更仔细的观察下，这种明显的简单性隐藏着显著的复杂性。Notch 信号依赖于广泛的机制，它除了核心转录机制外，还通过诱导和调节相邻细胞之间的通信来协调和控制细胞发育。一般来说，表达 Notch 受体的细胞可以通过相邻细胞上的配体在转导中被激活，导致转录和细胞命运的改变。然而，配体也有能力抑制 Notch 信号，当受体和配体在同一个细胞中顺式共表达时，就可以实现这种抑制。所谓的非经典 Notch 途径进一步多样化了 Notch 的潜在输出，并允许它协调对细胞生物学许多方面的调节。幸运的是，近年来，敲除小鼠和其他动物模型的产生和研究产生了大量关于 Notch 基因功能的新科学信息，允许解析特定 Notch 成分在人类发育和健康中的作用，并为预防和治疗包括癌症在内的各种独立疾病开辟了新的途径，尽管这一目标仍然具有挑战性。
