Glycolytic flux-signaling controls mouse embryo mesoderm development

Area of Science:

• Developmental Biology
• Metabolic Signaling
• Cellular Metabolism

Background:

• The relationship between cellular metabolic state and cellular programs remains a fundamental question.
• Understanding how metabolic pathways influence embryonic development is crucial for developmental biology.

Purpose of the Study:

• To investigate the impact of glycolytic flux on embryonic development, specifically presomitic mesoderm (PSM) patterning.
• To identify key metabolites linking glycolysis to developmental processes.

Main Methods:

• Utilized mouse embryos to identify fructose 1,6-bisphosphate (FBP) as a sentinel metabolite for glycolytic flux in PSM cells.
• Supplemented media with FBP and other glycolytic metabolites to assess effects on mesoderm segmentation.
• Generated a conditional mouse model for PFKFB3 overexpression to manipulate glycolytic flux and FBP levels.
• Performed subcellular proteome analysis to investigate changes in protein localization.

Main Results:

• FBP supplementation impaired mesoderm segmentation and downregulated Wnt signaling, mimicking effects of manipulated glycolytic flux.
• Overexpression of cytoplasmic PFKFB3 increased glycolytic flux and FBP levels, leading to similar developmental defects.
• FBP supplementation altered the subcellular localization of glycolytic enzymes, such as Pfkl and Aldoa, in PSM cells.

Conclusions:

• FBP acts as a flux-signaling metabolite connecting glycolysis to PSM patterning.
• FBP may exert its effects by modulating the subcellular localization of key proteins involved in developmental signaling pathways.