Lageentwicklung des Proepikards und des Mündungsabschnittes des Pulmonalvenenstammes bei Xenopus laevis

Abstract

INTRODUCTION. This study focuses on two aspects of the development of the venous heart pole that might be controlled by the specification of the left-right (L-R) body axis. These are (1) the development of the proepicardium (PE); and (2) the development of the veno-atrial connections. The PE is an embryonic progenitor cell population, which provides the epicardium, the majority of the cardiac interstitium, the coronary vasculature and possibly a sub-population of cardiomyocytes. Recent studies have documented the presence of bilaterally paired PE anlagen in several vertebrates, and species-specific differences in the fate of the left and right PE anlagen suggesting that PE development might depend on the specification of the L-R body axis. The mature heart of lung-breathing vertebrates normally shows an asymmetric arrangement of its veno-atrial connections along the L-R body axis. The systemic venous tributaries empty into the right atrium while the pulmonary venous tributaries empty into the left atrium. The ways by which this asymmetry evolves from the originally symmetrically arranged embryonic venous heart pole are poorly defined. Here, I document, for the first time, (1) the development of the PE and (2) the development of the veno-atrial connections in the frog Xenopus laevis, which is one of the most frequently used model organism in developmental biology. RESULTS 1. PE DEVELOPMENT (stages 37-46): The PE appears at stage 41 in the form of a cone-shaped accumulation of mesothelial cells covering the pericardial surface of the right horn of the sinus venosus. No such structure appears on the left sinus horn. At the end of stage 41, the tip of the cone-shaped PE establishes a firm contact with the right dorso-lateral border of the developing ventricle. Thereby, a secondary tissue bridge is established facilitating the transfer of PE cells to the heart. During stages 41-46, this cord-like tissue bridge is visible in vivo through the transparent body wall of the embryo. L-R lineage tracing using dextran-conjugated fluorescent dyes shows that the PE has a right-sided origin. RESULTS 2. DEVELOPMENT OF VENO-ATRIAL CONNECTIONS (stages 40-46): The venous pole of the embryonic heart is originally connected only to the systemic venous tributaries. Prior to the appearance of the mouth of the common pulmonary vein (MCPV), the systemic venous tributaries empty into a bilaterally symmetric chamber (sinus venosus) that is demarcated from the developing atriums by a circular ridge of tissue (sinu-atrial ridge). A solitary MCPV appears during stage 41. From the time point of its first appearance onwards, the MCPV lies cranial to the sinu-atrial ridge and to the left of the developing interatrial septum and body midline. L-R lineage tracing shows that the interatrial septum and MCPV both derive from the left body half. The common pulmonary vein, therefore, opens from the beginning into the future left atrium. The definitive veno-atrial connections are established by the formation of a septal complex that divides the lumen of the venous heart pole into systemic and pulmonary venous flow pathways. This complex arises from the anlage of the interatrial septum and the left half of the sinu-atrial ridge. CONCLUSIONS. These results show that, in Xenopus laevis, the formation of the PE and MCPV proceed in bilaterally asymmetric patterns as previously observed in chick embryos. I speculate that these bilaterally asymmetric patterns are controlled by signals from L-R signaling pathways and that the PE is an indicator for right-sidedness in Xenopus embryos. Since the L-R axis specification can be easily manipulated in frog embryos, Xenopus laevis might be a good model to uncover the role of L-R signaling pathways in the control of asymmetric formation of the PE and the MCPV.