Pulmonary endoderm, second heart field and the morphogenesis of distal outflow tract in mouse embryonic heart

The second heart field (SHF), foregut endoderm and sonic hedgehog (SHH) signaling pathway are all reported to associate with normal morphogenesis and septation of outflow tract (OFT). However, the morphological relationships of the development of foregut endoderm and expression of SHH signaling pathway members with the development of surrounding SHF and OFT are seldom described. In this study, serial sections of mouse embryos from ED9 to ED13 (midgestation) were stained with a series of marker antibodies for specifically highlighting SHF (Isl-1), endoderm (Foxa2), basement membrane (Laminin), myocardium (MHC) and smooth muscle (α-SMA) respectively, or SHH receptors antibodies including patched1 (Ptc1), patched2 (Ptc2) and smoothened, to observe the spatiotemporal relationship between them and their contributions to OFT morphogenesis. Our results demonstrated that the development of an Isl-1 positive field in the splanchnic mesoderm ventral to foregut, a subset of SHF, is closely coupled with pulmonary endoderm or tracheal groove, the Isl-1 positive cells surrounding pulmonary endoderm are distributed in a special cone-shaped pattern and take part in the formation of the lateral walls of the intrapericardial aorta and pulmonary trunk and the transient aortic-pulmonary septum, and Ptc1 and Ptc2 are exclusively expressed in pulmonary endoderm during this Isl-l positive field development, suggesting special roles played in inducing the Isl-l positive field formation by pulmonary endoderm. It is indicated that pulmonary endoderm plays a role in the development and specification of SHF in midgestation, and that pulmonary endoderm-associated Isl-l positive field is involved in patterning the morphogenesis and septation of the intrapericardial arterial trunks.