Atrial development in the human heart: An immunohistochemical study with emphasis on the role of mesenchymal tissues

The development of the atrial chambers in the human heart was investigated immunohistochemically using a set of previously described antibodies. This set included the monoclonal antibody 249-9G9, which enabled us to discrimin ate the endocardial cushion-derived mesenchymal tissues from those derived hom extracardiac splanchnic mesoderm, and a monoclonal antibody recognizing the B isoform of creatine kinase, which allowed us to distinguish the righ t atrial myocardium from the left. The expression patterns obtained with th ese antibodies, combined with additional histological information derived f rom the serial sections, permitted us to describe in detail the morphogenet ic events involved in the development of the primary atrial septum (septum primum) and the pulmonary vein in human embryos from Carnegie stage 14 onwa rd. The level of expression of creatine kinase B (CK-B) was found to be con sistently higher in the left atrial myocardium than in the right, with a sh arp boundary between high and low expression located between the primary se ptum and the left venous valve indicating that the primary septum is part o f the left atrial gene-expression domain. This expression pattern of CK-B i s reminiscent of that of the homeobox gene Pitx2, which has recently been s hown to be important for atrial septation in the mouse. This study also dem onstrates a poorly appreciated role of the dorsal mesocardium in cardiac de velopment. From the earliest stage investigated onward, the mesenchyme of t he dorsal mesocardium protrudes into the dorsal wall of the primary atrial segment. This dorsal mesenchymal protrusion is continuous with a mesenchyma l cap on the leading edge of the primary atrial septum. Neither the mesench ymal tissues of the dorsal protrusion nor the mesenchymal cap on the edge o f the primary septum expressed the endocardial tissue antigen recognized by 249-9G9 at any of the stages investigated. The developing pulmonary vein u ses the dorsal mesocardium as a conduit to reach the primary atrial segment . Initially, the pulmonary pit, which will becomes the portal of entry for the pulmonary vein, is located along the midline, flanked by two myocardial ridges. As development progresses, tissue remodeling results in the incorp oration of the portal of entry of the pulmonary vein in left atrial myocard ium, which is recognized because of its high level of creatine. Closure of the primary atrial foramen by the primary atrial septum occurs as a consequ ence of the fusion of these mesenchymal structures. Anat Rec 259:288-300, 2 000. (C) 2000 Wiley-Liss, Inc.