Pasini Andrea, Jiang Yun-Jin, Wilkinson David G
Division of Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 7AA, UK.
Development. 2004 Apr;131(7):1529-41. doi: 10.1242/dev.01031.
Alterations of the Delta/Notch signalling pathway cause multiple morphogenetic abnormalities in somitogenesis, including defects in intersomitic boundary formation and failure in maintenance of somite regularity. Notch signalling has been implicated in establishing the anteroposterior polarity within maturing somites and in regulating the activity of a molecular segmentation clock operating in the presomitic mesoderm. The pleiotropy of Notch signalling obscures the roles of this pathway in different steps of somitogenesis. One possibility is that distinct Notch effectors mediate different aspects of Notch signalling. In this study, we focus on two zebrafish Notch-dependent hairy/Enhancer-of-split-related transcription factors, Her6 and Her4, which are expressed at the transition zone between presomitic mesoderm and the segmented somites. The results of overexpression/gain-of-function and of morpholino-mediated loss-of-function experiments show that Her6 and Her4 are Notch signalling effectors that feedback on the clock and take part in the maintenance of cyclic gene expression coordination among adjacent cells in the presomitic mesoderm.
Delta/Notch信号通路的改变会在体节发生过程中导致多种形态发生异常，包括体节间边界形成缺陷和体节规律性维持失败。Notch信号通路与成熟体节内前后极性的建立以及调节前体节中胚层中运行的分子分割时钟的活性有关。Notch信号通路的多效性掩盖了该通路在体节发生不同步骤中的作用。一种可能性是不同的Notch效应器介导Notch信号通路的不同方面。在本研究中，我们聚焦于两种斑马鱼Notch依赖性毛发/分裂增强子相关转录因子Her6和Her4，它们在前体节中胚层和分节的体节之间的过渡区表达。过表达/功能获得实验以及吗啉代介导的功能丧失实验结果表明，Her6和Her4是Notch信号效应器，它们对时钟产生反馈，并参与前体节中胚层相邻细胞间循环基因表达协调的维持。
