Notch signaling is an evolutionarily highly conserved signaling mechanism, but in contrast to signaling pathways such as Wnt, Sonic Hedgehog, and BMP/TGF-β, Notch signaling occurs via cell-cell communication, where transmembrane ligands on one cell activate transmembrane receptors on a juxtaposed cell. Originally discovered through mutations in Drosophila more than 100 yr ago, and with the first Notch gene cloned more than 30 yr ago, we are still gaining new insights into the broad effects of Notch signaling in organisms across the metazoan spectrum and its requirement for normal development of most organs in the body. In this review, we provide an overview of the Notch signaling mechanism at the molecular level and discuss how the pathway, which is architecturally quite simple, is able to engage in the control of cell fates in a broad variety of cell types. We discuss the current understanding of how Notch signaling can become derailed, either by direct mutations or by aberrant regulation, and the expanding spectrum of diseases and cancers that is a consequence of Notch dysregulation. Finally, we explore the emerging field of Notch in the control of tissue homeostasis, with examples from skin, liver, lung, intestine, and the vasculature.

中文翻译：

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在发育，组织稳态和疾病中的Notch信号传导

Notch信号传导是一种进化上高度保守的信号传导机制，但与诸如Wnt，Sonic Hedgehog和BMP /TGF-β的信号传导途径相反，Notch信号传导是通过细胞-细胞通讯发生的，其中一个细胞上的跨膜配体激活了细胞上的跨膜受体。并列的细胞。最初是通过果蝇中的突变发现的一百多年前，随着第一个Notch基因的克隆在三十多年前，我们仍然获得了关于Notch信号在后生动物谱系中对生物的广泛影响及其对人体大多数器官正常发育的需求的新见解。 。在这篇综述中，我们提供了在分子水平上Notch信号传导机制的概述，并讨论了在结构上非常简单的途径如何能够参与多种细胞类型中细胞命运的控制。我们讨论了当前对Notch信号如何通过直接突变或异常调节脱轨以及Notch失调所致疾病和癌症范围扩大的理解。最后，我们以皮肤为例，探讨了Notch在控制组织动态平衡方面的新兴领域。