| O2 homeostasis is of critical importance during development. The cardiovascular system must constantly expand and remodel itself to ensure adequate delivery of O2 and nutrients to the increasing embryonic tissue mass. It has recently been demonstrated that low levels of O2 (hypoxia) activate the Hypoxia-Inducible Factor (HIF) complexes, which transcriptionally activate genes critical for all aspects of cardiovascular development. Mice deficient in the HIF subunit ARNT exhibit mid-gestational lethality from a variety of abnormalities. There is decreased proliferation of multilineage hematopoietic progenitors, stunted angiogenesis in the yolk sac and embryo, and a hypoplastic myocardium with absent endocardial cushion formation. In addition, there is decreased trophoblast stem cell proliferation and improper cell fate decisions leading to defective placentation. In vivo and in vitro work has verified the primary nature of the hematopoietic and placental defects, and has confirmed a role for ARNT in hypoxia signaling. This work therefore illustrates the important roles that environmental factors, such as O2 perform in the development of complex, multicellular organisms. |
