Essential role of p38α MAP kinase in placental but not embryonic cardiovascular development

p38 alpha MAP kinase is activated in response to many cellular stresses and also regulates the differentiation and/or survival of various cell types in vitro, including skeletal muscle cells and cardiomyocytes. Here we show that targeted inactivation of the mouse p38a gene results in embryonic lethality at midgestation correlating with a massive reduction of the myocardium and malformation of blood vessels in the head region. However, this defect appears to be secondary to insufficient oxygen and nutrient transfer across the placenta. When the placental defect was rescued, p38 alpha(-1) embryos developed to term and were normal in appearance. Our results indicate that p38 alpha is required for placental organogenesis but is not essential for other aspects of mammalian embryonic development.