Oxygen availability plays a critical role in embryonic development and stem cell function. Low oxygen levels are naturally present in developing embryos, and cells respond by activating hypoxia-inducible factors (HIFs) and other molecules that regulate oxygen homeostasis. These factors coordinate the development of blood vessels, placenta, nervous system, and other organs. Embryonic stem and progenitor cells often reside in hypoxic niches, and low oxygen levels regulate their differentiation. Recent studies have shown a link between factors regulating stem/progenitor cell behavior and HIFs, providing a molecular framework for hypoxic control of differentiation and cell fate. These findings have implications for therapies in tissue regeneration and disease. Oxygen levels influence development by regulating oxygen delivery systems, ensuring proper metabolic activity in resident cells. Genetic regulation of these responses is conserved across the animal kingdom. For example, the effects of oxygen on mammalian cardiovascular components share features with the tracheal system in Drosophila. Oxygen controls branching in tracheal development, with local signals from oxygen-starved cells regulating terminal branching. Similarly, mammalian vascular development is regulated by HIF, with VEGF being a dominant angiogenic factor produced by oxygen-starved cells. HIF-1α and HIF-2α are critical for vascular development and placental formation, with HIF-2α-deficient mice showing varied phenotypes depending on genetic background. Oxygen levels also influence bone morphogenesis, adipogenesis, and stem cell phenotypes. Hypoxia can promote or inhibit stem cell differentiation, with stem cells residing in complex microenvironments or "niches." Oxygen availability regulates hematopoietic and embryonic stem cells, with HSCs in adult mammals residing in bone marrow niches. Hypoxia is essential for maintaining the pluripotency of embryonic stem cells. Oxygen levels also influence stem cell behavior in various contexts, including cancer stem cells. HIFs regulate stem and progenitor cell differentiation, with HIF-1α and HIF-2α playing distinct roles. Hypoxia modulates Notch activity, Wnt signaling, and OCT4 expression, which are crucial for stem cell function. Oxygen availability also influences the endoplasmic reticulum (ER) stress response, which is important for cellular survival under hypoxic conditions. The mTOR pathway is another key regulator of embryonic development, with mTORC1 and mTORC2 playing roles in cell growth, survival, and metabolism. Overall, oxygen availability is essential for embryonic development and stem cell function, with HIFs and other pathways playing critical roles in regulating cell fate and differentiation. Understanding these mechanisms has implications for therapies in tissue regeneration and disease.Oxygen availability plays a critical role in embryonic development and stem cell function. Low oxygen levels are naturally present in developing embryos, and cells respond by activating hypoxia-inducible factors (HIFs) and other molecules that regulate oxygen homeostasis. These factors coordinate the development of blood vessels, placenta, nervous system, and other organs. Embryonic stem and progenitor cells often reside in hypoxic niches, and low oxygen levels regulate their differentiation. Recent studies have shown a link between factors regulating stem/progenitor cell behavior and HIFs, providing a molecular framework for hypoxic control of differentiation and cell fate. These findings have implications for therapies in tissue regeneration and disease. Oxygen levels influence development by regulating oxygen delivery systems, ensuring proper metabolic activity in resident cells. Genetic regulation of these responses is conserved across the animal kingdom. For example, the effects of oxygen on mammalian cardiovascular components share features with the tracheal system in Drosophila. Oxygen controls branching in tracheal development, with local signals from oxygen-starved cells regulating terminal branching. Similarly, mammalian vascular development is regulated by HIF, with VEGF being a dominant angiogenic factor produced by oxygen-starved cells. HIF-1α and HIF-2α are critical for vascular development and placental formation, with HIF-2α-deficient mice showing varied phenotypes depending on genetic background. Oxygen levels also influence bone morphogenesis, adipogenesis, and stem cell phenotypes. Hypoxia can promote or inhibit stem cell differentiation, with stem cells residing in complex microenvironments or "niches." Oxygen availability regulates hematopoietic and embryonic stem cells, with HSCs in adult mammals residing in bone marrow niches. Hypoxia is essential for maintaining the pluripotency of embryonic stem cells. Oxygen levels also influence stem cell behavior in various contexts, including cancer stem cells. HIFs regulate stem and progenitor cell differentiation, with HIF-1α and HIF-2α playing distinct roles. Hypoxia modulates Notch activity, Wnt signaling, and OCT4 expression, which are crucial for stem cell function. Oxygen availability also influences the endoplasmic reticulum (ER) stress response, which is important for cellular survival under hypoxic conditions. The mTOR pathway is another key regulator of embryonic development, with mTORC1 and mTORC2 playing roles in cell growth, survival, and metabolism. Overall, oxygen availability is essential for embryonic development and stem cell function, with HIFs and other pathways playing critical roles in regulating cell fate and differentiation. Understanding these mechanisms has implications for therapies in tissue regeneration and disease.