Critical requirement of ERK/MAPK signaling in respiratory tract development

The mammalian genome contains two ERK/MAP kinase kinase genes, Mek1 and Mek2, which encode dual-specificity kinases responsible for ERK/MAP kinase activation. To define the function of ERK/MAPK signaling pathway in lung development, we performed tissue-specific deletions of Mek1 function in a Mek2 null background. Inactivation of both Mek genes in mesenchyme resulted in several phenotypes including giant omphalocele, skeletal defects, pulmonary hypoplasia, abnormal trachea patterning, and death at birth. Microarray analysis with RNA extracted from lungs of E15.5 Dermo1+/Cre, Mek1+/flox;Mek2-/-;Dermo1+/Cre and Mek1flox/flox;Mek2-/-;Dermo1+/Cre embryos was performed to evaluate the molecular impact of the loss of all Mek alleles in mesenchyme on lung development. . Total RNA was isolated from lungs of E15.5 Dermo1+/Cre embryos (control), from E15.5 Mek1+/flox;Mek2- /-;Dermo1+/Cre embryos (experimental) and from E15.5 Mek1flox/flox;Mek2-/-;Dermo1+/Cre embryos (experimental). Four specimens were analyzed per genotype.