| First Author | O'Reilly VC | Year | 2014 |
| Journal | Dev Biol | Volume | 391 |
| Issue | 1 | Pages | 99-110 |
| PubMed ID | 24657234 | Mgi Jnum | J:213653 |
| Mgi Id | MGI:5585544 | Doi | 10.1016/j.ydbio.2014.03.005 |
| Citation | O'Reilly VC, et al. (2014) Gene-environment interaction demonstrates the vulnerability of the embryonic heart. Dev Biol 391(1):99-110 |
| abstractText | Mammalian embryos develop in a low oxygen environment. The transcription factor hypoxia inducible factor 1a (HIF1alpha) is a key element in the cellular response to hypoxia. Complete deletion of Hif1alpha from the mouse conceptus causes extensive placental, vascular and heart defects, resulting in embryonic lethality. However the precise role of Hif1alpha in each of these organ systems remains unknown. To further investigate, we conditionally-deleted Hif1alpha from mesoderm, vasculature and heart individually. Surprisingly, deletion from these tissues did not recapitulate the same severe heart phenotype or embryonic lethality. Placental insufficiency, such as occurs in the complete Hif1alpha null, results in elevated cellular hypoxia in mouse embryos. We hypothesized that subjecting the Hif1alpha conditional null embryos to increased hypoxic stress might exacerbate the effects of tissue-specific Hif1alpha deletion. We tested this hypothesis using a model system mimicking placental insufficiency. We found that the majority of embryos lacking Hif1alpha in the heart died when exposed to non-physiological hypoxia. This was a heart-specific phenomenon, as HIF1alpha protein accumulated predominantly in the myocardium of hypoxia-stressed embryos. Our study demonstrates the vulnerability of the heart to lowered oxygen levels, and that under such conditions of non-physiological hypoxia the embryo absolutely requires Hif1alpha to continue normal development. Importantly, these findings extend our understanding of the roles of Hif1alpha in cardiovascular development. |
