HIF-1α is essential for solid tumor formation and embryonic vascularization. This study demonstrates that loss of HIF-1α in embryonic stem (ES) cells leads to reduced solid tumor growth, which is correlated with decreased vascular endothelial growth factor (VEGF) production under hypoxia. HIF-1α null mutant embryos exhibit severe morphological defects, including lack of cephalic vascularization, reduced somite numbers, abnormal neural fold formation, and increased hypoxia. These findings highlight the critical role of HIF-1α in controlling both embryonic and tumorigenic responses to oxygenation changes. HIF-1α is a heterodimer consisting of HIF-1α and ARNT, which mediates the transcriptional response to hypoxia. Targeted null mutations of the HIF-1α gene in ES cells showed that HIF-1α is essential for the up-regulation of hypoxia-responsive genes, including glycolytic enzymes like phosphoglycerate kinase-1 (PGK) and lactate dehydrogenase A (LDH). HIF-1α null ES cells form teratocarcinomas that are significantly smaller than those from wild-type cells, indicating a role for HIF-1α in tumor growth. HIF-1α null embryos show reduced tumor mass, increased apoptosis, and abnormal vascularization. These embryos also exhibit increased hypoxia and apoptosis, as measured by the EF5 marker. The loss of HIF-1α leads to disorganized yolk sac vascularization and abnormal neural development, highlighting its role in embryonic vascularization and neural development. The study also shows that HIF-1α is essential for the regulation of VEGF expression, which is crucial for embryonic development. HIF-1α null embryos exhibit reduced VEGF expression, leading to impaired vascularization. The results indicate that HIF-1α is a key regulator of embryonic vascularization and tumor growth, and its loss leads to significant developmental and tumorigenic defects. The findings underscore the importance of HIF-1α in maintaining normal oxygenation and vascularization in both embryonic and tumor tissues.HIF-1α is essential for solid tumor formation and embryonic vascularization. This study demonstrates that loss of HIF-1α in embryonic stem (ES) cells leads to reduced solid tumor growth, which is correlated with decreased vascular endothelial growth factor (VEGF) production under hypoxia. HIF-1α null mutant embryos exhibit severe morphological defects, including lack of cephalic vascularization, reduced somite numbers, abnormal neural fold formation, and increased hypoxia. These findings highlight the critical role of HIF-1α in controlling both embryonic and tumorigenic responses to oxygenation changes. HIF-1α is a heterodimer consisting of HIF-1α and ARNT, which mediates the transcriptional response to hypoxia. Targeted null mutations of the HIF-1α gene in ES cells showed that HIF-1α is essential for the up-regulation of hypoxia-responsive genes, including glycolytic enzymes like phosphoglycerate kinase-1 (PGK) and lactate dehydrogenase A (LDH). HIF-1α null ES cells form teratocarcinomas that are significantly smaller than those from wild-type cells, indicating a role for HIF-1α in tumor growth. HIF-1α null embryos show reduced tumor mass, increased apoptosis, and abnormal vascularization. These embryos also exhibit increased hypoxia and apoptosis, as measured by the EF5 marker. The loss of HIF-1α leads to disorganized yolk sac vascularization and abnormal neural development, highlighting its role in embryonic vascularization and neural development. The study also shows that HIF-1α is essential for the regulation of VEGF expression, which is crucial for embryonic development. HIF-1α null embryos exhibit reduced VEGF expression, leading to impaired vascularization. The results indicate that HIF-1α is a key regulator of embryonic vascularization and tumor growth, and its loss leads to significant developmental and tumorigenic defects. The findings underscore the importance of HIF-1α in maintaining normal oxygenation and vascularization in both embryonic and tumor tissues.