The role of Foxc2 gene in lung development

Foxc2 gene is one of the forkhead transcriptional factors which are expressed in several embryonic tissues, and plays a significant role in vascularization. During investigation of the cardiovascular anomalies in Foxc2 knockout fetuses, we have found some abnormalities in the lung, although the relationship between Foxc2 gene and the developmental lung morphogenesis is unknown. In this study, we sought to characterize the fetal lung tissue in Foxc2 mutant mice. Mutant fetuses at embryonic days 15.5-18.5 of gestation were obtained from the mating between ICR- Foxc2 heterozygotes. (Control: Wild type littermates, WT). To characterize tissue morphology, cryo-sections (5µm) of the lung were made and stained either with hematoxylin-eosin or immunohistochemically for CD31, Type IV collagen, and CXCR4. As markers for the cell differentiation efficacy, pro-SPC, T1αwere used. Foxc2 null fetuses showed relatively thicker alveolar septums and narrower lumens, but there was almost no difference in the staining of septum with CD31 and Type IV collagen between mutants and WT fetuses. Since there was no significant difference in the number and distribution of Pro-SPC+ and T1α+ cells, the differentiation efficacy was relatively preserved in mutants. However, T1α+ cells in Foxc2 mutant was morphologically different from those in WT. Proximal T1α+ cells in the lung of Foxc2 mutant fetuses did not become flat as those of WT. Our data indicate that Foxc2 gene is also involved in the lung maturation, especially the development of T1α+ cells in the alveolar epithelium. As a next step, the Foxc2 gene expression in the lungs of the mutants is now under investigation.