Selective glucose metabolism guides mammalian gastrulation. During gastrulation, glucose metabolism is spatially and temporally regulated to direct cell fate and morphogenesis. Two waves of glucose metabolism are identified: the first through the hexosamine biosynthetic pathway (HBP) in the epiblast to drive fate acquisition, and the second via glycolysis to guide mesoderm migration and lateral expansion. These processes are linked to ERK activity, with distinct mechanisms in each wave. Metabolic signaling, beyond energy production, actively modulates developmental programs. The study challenges the view of metabolism as generic, showing its role in guiding cell fate and specialized functions during development. Gastrulation forms the body plan from a simple multicellular structure. Localized morphogen signals guide cell-fate decisions, but the precise mechanisms of integration are unclear. A 'gradient theory' proposed in 1915 suggests graded metabolism along an embryonic axis directs tissue patterning. Recent studies support this with metabolic signaling, where metabolic enzymes and metabolites modulate cellular and developmental programs. Regionalized glycolytic gradients in chick and mouse embryos indicate glycolysis can function independently of energy production during development. Despite these insights, questions remain about whether the mammalian embryo processes nutrients uniformly, how metabolic signaling links to morphogen pathways, and how these signals integrate during early post-implantation morphogenesis. The study reveals two spatiotemporally resolved waves of glucose uptake during mouse gastrulation. The first wave, through HBP, occurs in the epiblast to drive fate acquisition, while the second wave, via glycolysis, guides mesoderm migration. These waves are coupled to high ERK activity, with distinct regulation in each. The findings show that compartmentalized cellular metabolism is integral in guiding cell fate and specialized functions during development. The study also demonstrates that glucose metabolism via HBP is essential for mesoderm fate acquisition and maintenance, with HBP substrates like GlcNAc playing a critical role in ERK signaling and EMT processes. The study further links HBP to EMT in the posterior epiblast, showing that glucose metabolism through HBP is necessary for EMT and epiblast cell ingression into the primitive streak. HBP also mediates ERK signaling in mesoderm transition, with ERK activity being regulated by glucose metabolism. The study shows that HBP is involved in guiding cell-fate transitions within the epiblast but is not critical for cells once they ingress into the streak and specify toward mesoderm. Late-stage glycolytic enzymes may become important when cells adopt a stable mesodermal fate and begin their lateral migration. Finally, the study demonstrates that late-stage glycolysis supports mesoderm migration, with glycolytic pathway inhibition affecting mesoderm-specific cellular behaviors such as motility. The findings highlight the importance of metabolic signaling in embryogenesis, showing that glucose metabolism is not only 'life-sSelective glucose metabolism guides mammalian gastrulation. During gastrulation, glucose metabolism is spatially and temporally regulated to direct cell fate and morphogenesis. Two waves of glucose metabolism are identified: the first through the hexosamine biosynthetic pathway (HBP) in the epiblast to drive fate acquisition, and the second via glycolysis to guide mesoderm migration and lateral expansion. These processes are linked to ERK activity, with distinct mechanisms in each wave. Metabolic signaling, beyond energy production, actively modulates developmental programs. The study challenges the view of metabolism as generic, showing its role in guiding cell fate and specialized functions during development. Gastrulation forms the body plan from a simple multicellular structure. Localized morphogen signals guide cell-fate decisions, but the precise mechanisms of integration are unclear. A 'gradient theory' proposed in 1915 suggests graded metabolism along an embryonic axis directs tissue patterning. Recent studies support this with metabolic signaling, where metabolic enzymes and metabolites modulate cellular and developmental programs. Regionalized glycolytic gradients in chick and mouse embryos indicate glycolysis can function independently of energy production during development. Despite these insights, questions remain about whether the mammalian embryo processes nutrients uniformly, how metabolic signaling links to morphogen pathways, and how these signals integrate during early post-implantation morphogenesis. The study reveals two spatiotemporally resolved waves of glucose uptake during mouse gastrulation. The first wave, through HBP, occurs in the epiblast to drive fate acquisition, while the second wave, via glycolysis, guides mesoderm migration. These waves are coupled to high ERK activity, with distinct regulation in each. The findings show that compartmentalized cellular metabolism is integral in guiding cell fate and specialized functions during development. The study also demonstrates that glucose metabolism via HBP is essential for mesoderm fate acquisition and maintenance, with HBP substrates like GlcNAc playing a critical role in ERK signaling and EMT processes. The study further links HBP to EMT in the posterior epiblast, showing that glucose metabolism through HBP is necessary for EMT and epiblast cell ingression into the primitive streak. HBP also mediates ERK signaling in mesoderm transition, with ERK activity being regulated by glucose metabolism. The study shows that HBP is involved in guiding cell-fate transitions within the epiblast but is not critical for cells once they ingress into the streak and specify toward mesoderm. Late-stage glycolytic enzymes may become important when cells adopt a stable mesodermal fate and begin their lateral migration. Finally, the study demonstrates that late-stage glycolysis supports mesoderm migration, with glycolytic pathway inhibition affecting mesoderm-specific cellular behaviors such as motility. The findings highlight the importance of metabolic signaling in embryogenesis, showing that glucose metabolism is not only 'life-s