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

Publication date: 27 February 2017
Source:Developmental Cell, Volume 40, Issue 4
Author(s): Vinay Bulusu, Nicole Prior, Marteinn T. Snaebjornsson, Andreas Kuehne, Katharina F. Sonnen, Jana Kress, Frank Stein, Carsten Schultz, Uwe Sauer, Alexander Aulehla
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.

Graphical abstract

Teaser

Bulusu, Prior, Snaebjoernsson et al. identify a glycolytic activity gradient in the mouse embryo during presomitic mesoderm (PSM) development. Using a FRET-pyruvate sensor mouse model for real-time imaging of metabolite levels, they find that spatial metabolic differences are functionally relevant and intrinsically linked to PSM cell differentiation and development.


http://ift.tt/2mAAh1J