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

Dev Cell. 2017 Feb 27;40(4):331-341.e4. doi: 10.1016/j.devcel.2017.01.015.


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.

Keywords: aerobic glycolysis; mammalian embryonic development; metabolic gradients; metabolite sensor; presomitic mesoderm (PSM); real-time imaging; somites; stable isotope tracing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Carbon Isotopes
  • Pyruvic Acid
  • Glucose