Metabolic activities are selective modulators for individual segmentation clock processes

Mitsuhiro Matsuda (), Jorge Lázaro and Miki Ebisuya ()
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Mitsuhiro Matsuda: European Molecular Biology Laboratory (EMBL) Barcelona
Jorge Lázaro: European Molecular Biology Laboratory (EMBL) Barcelona
Miki Ebisuya: European Molecular Biology Laboratory (EMBL) Barcelona

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-56120-5

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