title: Spatiotemporal Analysis of a Glycolytic Activity Gradient Linked to Mouse Embryo Mesoderm Development.
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 from13C-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.
authors.affiliation: Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany; Cell Biology & Biophysics Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
authors.forename: Vinay
authors.initials: V
authors.lastname: Bulusu
authors.affiliation: Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Prior
authors.affiliation: Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
authors.forename: Marteinn T
authors.initials: MT
authors.lastname: Snaebjornsson
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kuehne
authors.affiliation: Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
authors.forename: Katharina F
authors.initials: KF
authors.lastname: Sonnen
authors.affiliation: Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Kress
authors.affiliation: Cell Biology & Biophysics Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Stein
authors.affiliation: Cell Biology & Biophysics Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Schultz
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Uwe
authors.initials: U
authors.lastname: Sauer
authors.affiliation: Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany. Electronic address: aulehla@embl.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Aulehla
mesh_terms: D000818:Animals; D002247:Carbon Isotopes; D002454:Cell Differentiation / Q000235:genetics; D003199:Computer Systems; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development; D031541:Fluorescence Resonance Energy Transfer; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D017403:In Situ Hybridization; D007700:Kinetics; D008648:Mesoderm / Q000196:embryology* / Q000378:metabolism*; D064688:Metabolic Flux Analysis; D055432:Metabolomics; D051379:Mice; D008954:Models, Biological; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D019289:Pyruvic Acid / Q000378:metabolism; D019170:Somites / Q000196:embryology / Q000378:metabolism; D062211:Spatio-Temporal Analysis
chemical_list: D002247:Carbon Isotopes; D019289:Pyruvic Acid; D005947:Glucose
keywords: aerobic glycolysis; mammalian embryonic development; metabolic gradients; metabolite sensor; presomitic mesoderm (PSM); real-time imaging; somites; stable isotope tracing