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A noncanonical role of glycolytic metabolites controlling the timing of mouse embryo segmentation

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Item Type:Article
Title:A noncanonical role of glycolytic metabolites controlling the timing of mouse embryo segmentation
Creators Name:Miyazawa, Hidenobu, Rada, Jona, Prior, Nicole, Sanchez, Paul Gerald Layague, Esposito, Emilia, Bunina, Daria, Girardot, Charles, Zaugg, Judith and Aulehla, Alexander
Abstract:Studies on the impact of metabolism on cell fate decisions are seeing a renaissance. However, a key challenge remains to distinguish signaling functions of metabolism from its canonical bioenergetic and biosynthetic roles, which underlie cellular homeostasis. Here, we tackled this challenge using mouse embryonic axis segmentation as an experimental model. First, we found that energetically subminimal amounts of glucose can support ongoing segmentation clock activity, providing evidence that glycolysis exerts a signaling function. Using a dynamical systems approach based on entrainment, we identified fructose 1,6-bisphosphate (FBP) as the potential signaling metabolite. Functionally, we demonstrated that glycolytic flux/FBP control the segmentation clock period and Wnt signaling in an anticorrelated manner. Critically, we showed that the slow segmentation clock phenotype caused by elevated glycolysis is mediated by Wnt signaling rather than cellular bioenergetic and biosynthetic state. Combined, our results demonstrate a modular organization of metabolic functions, revealing a signaling module of glycolysis that can be decoupled from its canonical metabolic functions.
Keywords:Body Patterning, Embryonic Development, Energy Metabolism, Fructosediphosphates, Glucose, Glycolysis, Mammalian Embryo, Wnt Signaling Pathway, Animals, Mice
Source:Science Advances
ISSN:2375-2548
Publisher:American Association for the Advancement of Science
Volume:11
Number:38
Page Range:eadz9606
Date:19 September 2025
Official Publication:https://doi.org/10.1126/sciadv.adz9606
PubMed:View item in PubMed
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