Evidence for non-canonical roles of glucose metabolism in the embryo

In our lab we study the effects of glycolytic flux on development and specifically gene activity. Currently it is known that changes in the embryonic environment such as high glucose in diabetic pregnancies increases the risk of congenital malformations including heart, neural tube and segmentation defects. To investigate the link between glucose metabolism and development we use mouse segmentation as a model. We culture mesodermal explants in a chemically defined medium and add glycolytic intermediates in order to bypass or increase the load on specific enzymes. As a real-time readout for gene activity we monitor the oscillatory expression of a venus reporter driven by the promoter of the lunatic fringe gene in the presomitic mesoderm (PSM) during somitogenesis. To date we have identified conditions in which explants cultured with specific metabolites display altered states of gene activity. We have evidence to suggest altered gene activity is not due to a canonical function of carbohydrate metabolism. Additionally we have found minimal flux through the glycolytic enzyme PFK (phosphofructokinase) a flux regulator, to be required for normal PSM patterning. We propose glucose metabolism has a non-canonical role in regulating embryogenesis and the mechanism may be mediated via the activity of PFK.