Department of Biochemistry and Molecular Biology, Cumming School of Medicine, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.
Elife. 2019 Aug 27;8:e49252. doi: 10.7554/eLife.49252.
Spinal cord patterning is orchestrated by multiple cell signalling pathways. Neural progenitors are maintained by Notch signalling, whereas ventral neural fates are specified by Hedgehog (Hh) signalling. However, how dynamic interactions between Notch and Hh signalling drive the precise pattern formation is still unknown. We applied the PHRESH (otoconvertible porter of ignalling istory) technique to analyse cell signalling dynamics in vivo during zebrafish spinal cord development. This approach reveals that Notch and Hh signalling display similar spatiotemporal kinetics throughout spinal cord patterning. Notch signalling functions upstream to control Hh response of neural progenitor cells. Using gain- and loss-of-function tools, we demonstrate that this regulation occurs not at the level of upstream regulators or primary cilia, but rather at the level of Gli transcription factors. Our results indicate that Notch signalling maintains Hh responsiveness of neural progenitors via a Gli-dependent mechanism in the spinal cord.
脊髓模式形成由多种细胞信号通路协调。Notch 信号维持神经祖细胞，而 Hedgehog（Hh）信号则指定腹侧神经命运。然而，Notch 和 Hh 信号之间的动态相互作用如何驱动精确的模式形成仍然未知。我们应用 PHRESH（信号历史的可转换 porter）技术来分析斑马鱼脊髓发育过程中的体内细胞信号动力学。这种方法表明，Notch 和 Hh 信号在整个脊髓模式形成过程中表现出相似的时空动力学。Notch 信号在前馈途径中起作用，以控制神经祖细胞的 Hh 反应。使用增益和功能丧失工具，我们证明这种调节不是在上游调节剂或初级纤毛的水平上发生，而是在 Gli 转录因子的水平上发生。我们的结果表明，Notch 信号通过 Gli 依赖的机制在脊髓中维持神经祖细胞的 Hh 反应性。
