Early development of the pulmonary vascular system: An anatomical and histochemical reinvestigation of the pulmonary venous return development in mice

Pulmonary venous return development establishes the fetal circulation and is critical for the formation of pulmonary circulation independent of systemic circulation at birth. Anomalous returns lead to inappropriate drainage of blood flow, sometimes resulting in neonatal cyanosis and cardiac failure. While many classical studies have discussed the anatomical features of the pulmonary venous system development, the cellular dynamics of the endothelia based on the molecular marker expression remain unknown. In the present study, we examined the expression of several endothelial markers during early pulmonary vascular system development of murine embryos. We show that Endomucin and CD31 are expressed early in endothelial cells of the splanchnic plexus, which is the precursor of the pulmonary vascular system. Three-dimensional analyses of the expression patterns revealed the spatiotemporal modification of the venous returns to systemic venous systems or sinoatrial canal during the formation of the pulmonary plexus. We herein report the results of spatiotemporal analyses of the early pulmonary venous system development with histochemistry as well as a delineation of the anatomical features of the tentative drainage pathways.