The role of oxygen availability in embryonic development and stem cell function

Abstract

Changes in oxygen (O₂) tensions clearly have a role in patterning invertebrate and vertebrate embryos. One of the first examples of the impact of O₂ availability on developmental processes was demonstrated for the Drosophila melanogaster tracheal system. Here, O₂-starved cells provide signals that promote increased branching morphogenesis of the O₂-delivering tracheal network. Genetic evidence now indicates that the differentiation of mammalian cardiovascular, placental, pulmonary, bone and haematopoietic cells and adipocytes is regulated by O₂ availability. Various pathways that mediate responses to O₂ deprivation (hypoxia) have a role in embryonic development. The best genetic evidence is provided by animals that lack various subunits of the hypoxia inducible factor (HIF) heterodimeric transcription factors. Recently, stem and progenitor cell phenotypes have been shown to be regulated by changes in O₂ levels. Once again, HIFs have a crucial role in this process by interfacing with other stem cell signalling pathways such as those involving OCT4, Notch and Wnt.