Development of the Myocardium of the Atrioventricular Canal and the Vestibular Spine in the Human Heart

Abstract

To establish the morphogenetic mechanisms underlying formation and separation of the atrioventricular connections, we studied the remodeling of the myocardium of the atrioventricular canal and the extracardiac mesenchymal tissue of the vestibular spine in human embryonic hearts from 4.5 to 10 weeks of development. Septation of the atrioventricular junction is brought about by downgrowth of the primary atrial septum, fusion of the endocardial cushions, and forward expansion of the vestibular spine between atrial septum and cushions. The vestibular spine subsequently myocardializes to form the ventral rim of the oval fossa. The connection of the atrioventricular canal with the atria expands evenly. In contrast, the expression patterns of creatine kinase M and GlN2, markers for the atrioventricular and interventricular junctions, respectively, show that the junction of the canal with the right ventricle forms by local growth in the inner curvature of the heart. Growth of the caudal portion of the muscular ventricular septum to make contact with the inferior endocardial cushion occurs only after the canal has expanded rightward. The atrioventricular node develops from that part of the canal myocardium that retains its continuity with the ventricular myocardium.

A spatiotemporal evaluation of the contribution of the dorsal mesenchymal protrusion to cardiac development

“…These studies revealed important associations between the development of the DMP and the atrial and AV septal structures (Tasaka et al, 1996;Webb et al, 1998b;Anderson et al, 1999;Wessels et al, 2000;Kim et al, 2001). The importance of the DMP was further emphasized by work linking abnormal DMP development to AV sep- The boxed area in A is shown at a higher magnification.…”

“…Significant strides in our understanding of the DMP, and its potential importance to heart development, were made in studies utilizing techniques such as standard histology, immunohistochemistry, and electron microscopy (Tasaka et al, 1996;Webb et al, 1998b;Anderson et al, 1999;Wessels et al, 2000;Kim et al, 2001). These studies revealed important associations between the development of the DMP and the atrial and AV septal structures (Tasaka et al, 1996;Webb et al, 1998b;Anderson et al, 1999;Wessels et al, 2000;Kim et al, 2001).…”

“…tal defects in human cases and animal models of Down Syndrome (Tasaka et al, 1996;Webb et al, 1999;Blom et al, 2003). Due to the intimate relationship of the DMP with the endocardial-derived cushion tissues, determining the extent of the DMP in relation to these tissues has been a subject of much disagreement (Tasaka et al, 1996;Webb et al, 1998b;Wessels et al, 2000;Kim et al, 2001). Thus, studies to delineate the DMP have long been hampered by the absence of molecular tools to mark the DMP specifically and by the fact that experimental cell-fate tracing techniques, such as those used to study the contribution of the neural crest Waldo et al, 1999) and the epicardium (Gittenberger-de PerezPomares et al, 2002) to heart development, are not (yet) feasible for this particular structure.…”

“…In addition, extracardiac mesenchyme associated with the dorsal mesocardium, contributes to the mesenchymal cell-mass at the venous pole of the heart. Historically, this mesenchyme has been referred to with terms such as spina vestibuli (or vestibular spine) (Tasaka et al, 1996;Anderson et al, 1999;Kim et al, 2001;Mommersteeg et al, 2006;His, 1880), endocardial proliferation of the dorsal mesocardium (Chang, 1931), sinus venosus tissue (Van Praagh and Corsini, 1969), and mesenchymatous tissue (van Gils, 1981). Given the histological characteristics of the mesenchyme, i.e., it is a mesenchymal tissue that protrudes into the dorsal aspect of the atrial cavity, we have dubbed it the "dorsal mesenchymal protrusion (DMP)," as this more accurately describes its specific features relevant to the development and architecture of the heart .…”

“…While it is generally accepted that normal AV septation includes the complete fusion of the DMP and mesenchymal cap with the superior and inferior AV cushions, resulting in the formation of the AV mesenchymal complex and the closure of the primary atrial foramen (Webb et al, 1998a;Anderson et al, 1999), the origin of the DMP and the extent of its contribution to the AV mesenchymal complex have been controversial (Tasaka et al, 1996;Webb et al, 1998b;Wessels et al, 2000;Kim et al, 2001). Studies of the DMP in heart development have previously relied upon anatomical relationships and histological analyses of the DMP and surrounding tissues (Webb et al, 1998a,b;Anderson et al, 1999;Wessels et al, 2000;Kim et al, 2001;His, 1880). The importance of understanding the origin and fate of the DMP is underscored by indications of a potential role for the DMP in atrioventricular septal defect (AVSD) pathology (Tasaka et al, 1996;Webb et al, 1999;Blom et al, 2003).…”