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

Vinay Bulusu, Nicole Prior, Marteinn T. Snaebjornsson, Andreas Kuehne, Katharina F. Sonnen, Jana Kress, Frank Stein, Carsten Schultz, Uwe Sauer, Alexander Aulehla

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)331-341.e4
JournalDevelopmental Cell
Volume40
Issue number4
DOIs
StatePublished - Feb 27 2017

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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