Metabolic reprogramming promotes neural crest migration via Yap/Tead signaling

The Warburg effect is one of the metabolic hallmarks of cancer cells, characterized by enhanced glycolysis even under aerobic conditions. While this physiological adaptation is associated with metastatic behavior, we still have a superficial understanding of how it affects cell motility in development and disease. Here we report that the neural crest, a migratory stem cell population in vertebrate embryos, undergoes an extensive metabolic remodeling to engage in aerobic glycolysis prior to delamination. This increase in glycolytic flux promotes Yap/Tead signaling, which directly activates the expression of a set of transcription factors to drive epithelial-to-mesenchymal transition. Our results demonstrate how shifts in carbon metabolism can trigger the gene regulatory circuits that control complex cell behaviors. Our findings also support the hypothesis that the Warburg effect is a tightly regulated developmental mechanism that is anomalously reactivated during tumorigenesis and metastasis.