Oscillatory links of Fgf signaling and Hes7 in the segmentation clock
Oscillatory links of Fgf signaling and Hes7 in the segmentation clock
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DOI：
10.1016/j.gde.2013.02.005
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发表时间：
2013-08-01
影响因子：
4
通讯作者：
Kageyama, Ryoichiro
中科院分区：
文献类型：
--
作者：
Harima, Yukiko;Kageyama, Ryoichiro
体节发生是由分割时钟控制的，其中周期基因如Hes 7的振荡表达导致体节形成的主基因Mesp 2的周期性表达。Fgf信号传导诱导Hes 7的振荡表达，而Hes 7驱动Fgf和Notch信号传导中的耦合振荡，其分别抑制和激活Mesp 2表达。由于不同的振荡动力学，Fgf信号传导中的振荡与S-1中Notch信号传导中的振荡分离，S-1是一个潜在的体节区域，其中Notch信号传导在Fgf信号传导关闭时诱导Mesp 2表达。因此，Fgf信号的振荡调节Mesp 2表达的时间和体节发生的速度。此外，发现Fgf信号传导是缺氧的主要靶点，缺氧导致Hes 7或Mesp 2中杂合突变的表型变异，表明通过该信号传导的基因-环境相互作用。
Somitogenesis is controlled by the segmentation clock, where the oscillatory expression of cyclic genes such as Hes7 leads to the periodic expression of Mesp2, a master gene for somite formation. Fgf signaling induces the oscillatory expression of Hes7 while Hes7 drives coupled oscillations in Fgf and Notch signaling, which inhibits and activates Mesp2 expression, respectively. Because of different oscillatory dynamics, oscillation in Fgf signaling dissociates from oscillation in Notch signaling in S-1, a prospective somite region, where Notch signaling induces Mesp2 expression when Fgf signaling becomes off. Thus, oscillation in Fgf signaling regulates the timing of Mesp2 expression and the pace of somitogenesis. In addition, Fgf signaling was found to be a primary target for hypoxia, which causes phenotypic variations of heterozygous mutations in Hes7 or Mesp2, suggesting gene-environment interaction through this signaling.