The study investigates the role of glucose metabolism in guiding mammalian gastrulation, a critical stage of embryonic development. Using single-cell-resolution quantitative imaging, the researchers identify two distinct waves of glucose metabolism during gastrulation: the first wave, driven by the hexosamine biosynthetic pathway (HBP), occurs in the epiblast and drives fate acquisition, while the second wave, driven by glycolysis, guides mesoderm migration and lateral expansion. The study demonstrates that glucose metabolism influences these developmental processes through cellular signaling pathways, particularly by modulating ERK activity in each wave. The findings highlight the importance of compartmentalized cellular metabolism in shaping cell fate and specialized functions during development, challenging the traditional view of cellular metabolism as merely a housekeeping function. The research provides valuable insights into the roles of metabolic signaling in various developmental contexts and supports the 'gradient theory' of embryonic patterning.The study investigates the role of glucose metabolism in guiding mammalian gastrulation, a critical stage of embryonic development. Using single-cell-resolution quantitative imaging, the researchers identify two distinct waves of glucose metabolism during gastrulation: the first wave, driven by the hexosamine biosynthetic pathway (HBP), occurs in the epiblast and drives fate acquisition, while the second wave, driven by glycolysis, guides mesoderm migration and lateral expansion. The study demonstrates that glucose metabolism influences these developmental processes through cellular signaling pathways, particularly by modulating ERK activity in each wave. The findings highlight the importance of compartmentalized cellular metabolism in shaping cell fate and specialized functions during development, challenging the traditional view of cellular metabolism as merely a housekeeping function. The research provides valuable insights into the roles of metabolic signaling in various developmental contexts and supports the 'gradient theory' of embryonic patterning.