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Spatiotemporal Analysis of a Glycolytic Activity Gradient Linked to Mouse Embryo Mesoderm Development.

Developmental cell | Feb 27, 2017

How metabolism is rewired during embryonic development is still largely unknown, as it remains a major technical challenge to resolve metabolic activities or metabolite levels with spatiotemporal resolution. Here, we investigated metabolic changes during development of organogenesis-stage mouse embryos, focusing on the presomitic mesoderm (PSM). We measured glycolytic labeling kinetics from 13C-glucose tracing experiments and detected elevated glycolysis in the posterior, more undifferentiated PSM. We found evidence that the spatial metabolic differences are functionally relevant during PSM development. To enable real-time quantification of a glycolytic metabolite with spatiotemporal resolution, we generated a pyruvate FRET-sensor reporter mouse line. We revealed dynamic changes in cytosolic pyruvate levels as cells transit toward a more anterior PSM state. Combined, our approach identifies a gradient of glycolytic activity across the PSM, and we provide evidence that these spatiotemporal metabolic changes are intrinsically linked to PSM development and differentiation.

Pubmed ID: 28245920 RIS Download

Mesh terms: Animals | Carbon Isotopes | Cell Differentiation | Computer Systems | Embryo, Mammalian | Embryonic Development | Fluorescence Resonance Energy Transfer | Gene Expression Regulation, Developmental | Genes, Reporter | Glucose | Glycolysis | In Situ Hybridization | Kinetics | Mesoderm | Metabolic Flux Analysis | Metabolomics | Mice | Models, Biological | Organ Specificity | Phenotype | Pyruvic Acid | Somites | Spatio-Temporal Analysis

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