Li Zhixing, Ruan Lingjuan, Lin Shuibin, Gittes George K
Department of Biomedical Science, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, PR China.
Biochem Biophys Res Commun. 2007 Aug 3;359(3):491-6. doi: 10.1016/j.bbrc.2007.05.156. Epub 2007 May 30.
The oscillations of circadian genes control the daily circadian clock, regulating a diverse array of physiologies with the 24-hour light/dark cue across a wide variety of organisms. Here we first show that before embryonic circadian rhythms occur, the oscillation (nucleocytoplasmic shuttling) of core circadian gene Clock is tissue-specific and correlated with the state of differentiation during both early development and later pancreas organogenesis. Disruption of Clock as well as Timeless in the embryonic pancreas does not block pancreatic differentiation but alters the balance and maturity of endocrine and exocrine cells. Molecular analysis indicates that inhibition of Clock or Timeless expression disturbs not only cell cycle regulators, but also Wnt- and Notch-signaling components, whose oscillations establish the timing mechanism in somitogenesis. Thus, our results provide new insights about circadian genes' function in control of the timing of differentiation during embryonic development.
昼夜节律基因的振荡控制着日常的生物钟，通过24小时的光/暗信号在各种各样的生物体中调节一系列不同的生理过程。在这里，我们首先表明，在胚胎昼夜节律出现之前，核心昼夜节律基因Clock的振荡（核质穿梭）具有组织特异性，并且在早期发育和后期胰腺器官发生过程中都与分化状态相关。胚胎胰腺中Clock以及Timeless的破坏不会阻止胰腺分化，但会改变内分泌和外分泌细胞的平衡和成熟度。分子分析表明，Clock或Timeless表达的抑制不仅会干扰细胞周期调节因子，还会干扰Wnt和Notch信号成分，它们的振荡在体节发生中建立了时间机制。因此，我们的结果为昼夜节律基因在胚胎发育过程中控制分化时间的功能提供了新的见解。
