Hypoxia-inducible factor 1α (HIF-1α) is a key regulator of oxygen homeostasis in cells and during development. This study shows that in HIF-1α-deficient embryonic stem (ES) cells, the expression of genes involved in glucose transport and glycolysis is reduced, and cellular proliferation is impaired. HIF-1α deficiency also leads to decreased vascular endothelial growth factor (VEGF) expression and developmental arrest in embryos, resulting in neural tube defects, cardiovascular malformations, and cell death in the cephalic mesenchyme. In contrast, HIF-1α expression increases in embryos as developmental defects and cell death occur in HIF-1α-deficient embryos. These findings demonstrate that HIF-1α is a master regulator of oxygen homeostasis, essential for normal development and physiological function. HIF-1α is uniquely expressed in response to hypoxia and regulates the expression of genes involved in oxygen homeostasis, including those encoding glucose transporters, glycolytic enzymes, and VEGF. The study also shows that HIF-1α deficiency leads to severe developmental defects, including abnormal vascularization, neural tube closure, and mesenchymal cell death. These results highlight the critical role of HIF-1α in maintaining oxygen homeostasis during embryonic development and in the formation of key physiological systems. The study provides evidence that HIF-1α is required for proper cardiovascular development and embryonic cell survival. The findings suggest that HIF-1α is a master regulator of oxygen homeostasis, essential for normal development and physiological function.Hypoxia-inducible factor 1α (HIF-1α) is a key regulator of oxygen homeostasis in cells and during development. This study shows that in HIF-1α-deficient embryonic stem (ES) cells, the expression of genes involved in glucose transport and glycolysis is reduced, and cellular proliferation is impaired. HIF-1α deficiency also leads to decreased vascular endothelial growth factor (VEGF) expression and developmental arrest in embryos, resulting in neural tube defects, cardiovascular malformations, and cell death in the cephalic mesenchyme. In contrast, HIF-1α expression increases in embryos as developmental defects and cell death occur in HIF-1α-deficient embryos. These findings demonstrate that HIF-1α is a master regulator of oxygen homeostasis, essential for normal development and physiological function. HIF-1α is uniquely expressed in response to hypoxia and regulates the expression of genes involved in oxygen homeostasis, including those encoding glucose transporters, glycolytic enzymes, and VEGF. The study also shows that HIF-1α deficiency leads to severe developmental defects, including abnormal vascularization, neural tube closure, and mesenchymal cell death. These results highlight the critical role of HIF-1α in maintaining oxygen homeostasis during embryonic development and in the formation of key physiological systems. The study provides evidence that HIF-1α is required for proper cardiovascular development and embryonic cell survival. The findings suggest that HIF-1α is a master regulator of oxygen homeostasis, essential for normal development and physiological function.