Matsuda Mitsuhiro, Lázaro Jorge, Ebisuya Miki
European Molecular Biology Laboratory (EMBL) Barcelona, Barcelona, Spain.
Cluster of Excellence Physics of Life, TU Dresden, Dresden, Germany.
Nat Commun. 2025 Jan 20;16(1):845. doi: 10.1038/s41467-025-56120-5.
Numerous cellular and molecular processes during embryonic development prompt the fundamental question of how their tempos are coordinated and whether a common global modulator exists. While the segmentation clock tempo scales with the kinetics of gene expression and degradation processes of the core clock gene Hes7 across mammals, the coordination of these processes remains unclear. This study examines whether metabolic activities serve as a global modulator for the segmentation clock, finding them to be selective instead. Several metabolic inhibitions extend the clock period but affect key processes differently: glycolysis inhibition slows Hes7 protein degradation and production delay without altering intron delay, while electron transport chain inhibition extends intron delay without influencing the other processes. Combinations of distinct metabolic inhibitions exhibit synergistic effects. We propose that the scaled kinetics of segmentation clock processes across species may result from combined selective modulators shaped by evolutionary constraints, rather than a single global modulator.
胚胎发育过程中的众多细胞和分子过程引发了一个基本问题，即它们的节奏是如何协调的，以及是否存在一种共同的全局调节因子。虽然跨哺乳动物的体节时钟节奏与核心时钟基因Hes7的基因表达和降解过程的动力学相关，但这些过程的协调仍不清楚。本研究考察了代谢活动是否作为体节时钟的全局调节因子，结果发现它们具有选择性。几种代谢抑制会延长时钟周期，但对关键过程的影响不同：糖酵解抑制减缓了Hes7蛋白降解和产生延迟，而不改变内含子延迟，而电子传递链抑制则延长内含子延迟，而不影响其他过程。不同代谢抑制的组合表现出协同效应。我们提出，跨物种的体节时钟过程的缩放动力学可能是由进化限制塑造的组合选择性调节因子导致的，而不是单一的全局调节因子。
