Metabolic Reprogramming Promotes Neural Crest Migration via Yap/Tead Signaling

• Published in: Developmental cell 2020-04, Vol.53 (2), p.199-211.e6
• Main Authors: Bhattacharya, Debadrita, Azambuja, Ana Paula, Simoes-Costa, Marcos
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; cell metabolism; cell migration; Cell Movement; Chick Embryo; Chickens; epithelial to mesenchymal transition; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Developmental; Glycolysis; neural crest; Neural Crest - physiology; Organ Specificity; Transcription Factors - genetics; Transcription Factors - metabolism; Warburg effect; Yap/Tead signaling
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2020.03.005

The Warburg effect is one of the metabolic hallmarks of cancer cells, characterized by enhanced glycolysis even under aerobic conditions. This physiological adaptation is associated with metastasis , but we still have a superficial understanding of how it affects cellular processes during embryonic development. 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 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. These findings support the hypothesis that the Warburg effect is a precisely regulated developmental mechanism that is anomalously reactivated during tumorigenesis and metastasis. [Display omitted] •Neural crest cells display the metabolic adaptation known as the Warburg effect•Enhanced glycolysis is required for neural crest epithelial-to-mesenchymal transition•Aerobic glycolysis promotes cell motility via the Yap/Tead signaling pathway•Yap/Tead interact with tissue-specific enhancers to promote neural crest migration Cancer cells display the Warburg effect, a metabolic adaptation characterized by enhanced glycolysis under aerobic conditions. Bhattacharya et al. demonstrate that this physiological adaptation is required for migration of neural crest cells in vertebrate embryos. Their results indicate that aerobic glycolysis is a developmental mechanism that is co-opted by metastatic cells.