University College London, The Ear Institute, London, UK.
Adv Exp Med Biol. 2020;1218:129-157. doi: 10.1007/978-3-030-34436-8_8.
Notch signalling is a major regulator of cell fate decisions and tissue patterning in metazoans. It is best known for its role in lateral inhibition, whereby Notch mediates competitive interactions between cells to limit adoption of a given developmental fate. However, it can also function by lateral induction, a cooperative mode of action that was originally described during the patterning of the Drosophila wing disc and creates boundaries or domains of cells of the same character. In this chapter, we introduce these two signalling modes and explain how they contribute to distinct aspects of the development and regeneration of the vertebrate inner ear, the organ responsible for the perception of sound and head movements. We discuss some of the factors that could influence the context-specific outcomes of Notch signalling in the inner ear and the ongoing efforts to target this pathway for the treatment of hearing loss and vestibular dysfunction.
Notch 信号通路是后生动物细胞命运决定和组织模式形成的主要调控因子。它最著名的作用是在侧向抑制中,Notch 介导细胞之间的竞争相互作用,以限制特定发育命运的采用。然而,它也可以通过侧向诱导发挥作用,这是一种合作作用模式,最初在果蝇翅膀盘的模式形成中被描述,并创建具有相同特征的细胞的边界或域。在本章中,我们介绍这两种信号模式,并解释它们如何有助于脊椎动物内耳发育和再生的不同方面,内耳是负责感知声音和头部运动的器官。我们讨论了一些可能影响内耳中 Notch 信号通路特定于上下文的结果的因素,以及靶向该途径治疗听力损失和前庭功能障碍的持续努力。