Cardiac septation: a late contribution of the embryonic primary myocardium to heart morphogenesis

Cardiac septation: a late contribution of the embryonic primary myocardium to heart morphogenesis. Lamers WH, Moorman AF. Department of Anatomy and Embryology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. [email protected] Heart morphogenesis comprises 2 major consecutive steps, viz. chamber formation followed by septation. Septation is the remodeling of the heart from a single-channel peristaltic pump to a dual-channel, synchronously contracting device with 1-way valves. In the human heart, septation occurs between 4 and 7 weeks of development. Cardiac looping and chamber formation bring the contributing structures into position to engage in septation. Cardiomyocytes that participate in chamber formation do not materially contribute to septation. The (re)discovery of the role of extracardiac mesenchymal tissue in atrioventricular septation, the appreciation that the formation of the right atrioventricular connection is more than a mere rightward expansion of the atrioventricular canal, the awareness that myocardium originating from the so-called anterior heart field regresses after its function as outflow-tract sphincter ceases, and the recent finding that the myocardialized proximal portion of the outflow-tract septum becomes the supraventricular crest have all significantly enhanced our understanding of the morphogenetic processes that contribute to septation. The bifurcation of the ventricular conduction system is the landmark that separates the contribution of the atrioventricular cushions and the outflow-tract ridges to septation and that divides the muscular ventricular septum in inlet, trabecular, and outlet portions

Development of the myocardium of the atrioventricular canal and the vestibular spine in the human heart

Development of the myocardium of the atrioventricular canal and the vestibular spine in the human heart. Kim JS, Viragh S, Moorman AF, Anderson RH, Lamers WH. Department of Anatomy & Embryology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 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 myocardiu

MLC3F transgene expression in iv mutant mice reveals the importance of left-right signalling pathways for the acquisition of left and right atrial but not ventricular compartment identity

Abstract Transcriptional differences between left and right cardiac chambers are revealed by an nlacZ reporter transgene controlled by regulatory sequences of the MLC3F gene, which is expressed in the left ventricle (LV), atrioventricular canal (AVC), and right atrium (RA). To examine the role of left-right signalling in the acquisition of left and right chamber identity, we have investigated MLC3F transgene expression in iv mutant mice. iv/iv mice exhibit randomised direction of heart looping and an elevated frequency of associated laterality defects, including atrial isomerism. At fetal stages, 3F-nlacZ-2E transgene expression remains confined to the morphological LV, AVC, and RA in L-loop hearts, although these appear on the opposite side of the body. In cases of morphologically distinguishable right atrial appendage isomerism, both atrial appendages show strong transgene expression. Conversely, specimens with morphological left atrial appendage isomerism show only weak expression in both atrial appendages. The earliest left-right atrial differences in the expression of the 3F-nlacZ-2E transgene are observed at E8.5. DiI labelling experiments confirmed that transcriptional regionalisation of the 3F-nlacZ-2E transgene at this stage reflects future atrial chamber identity. In some iv/iv embryos at E8.5, the asymmetry of 3F-nlacZ-2E expression was lost, suggesting atrial isomerism at the transcriptional level prior to chamber formation. These data suggest that molecular specification of left and right atrial but not ventricular chambers is dependent on left-right axial cue

Three-dimensional and molecular analysis of the arterial pole of the developing human heart

Labeling experiments in chicken and mouse embryos have revealed important roles for different cell lineages in the development of the cardiac arterial pole. These data can only fully be exploited when integrated into the continuously changing morphological context and compared with the patterns of gene expression. As yet, studies on the formation of separate ventricular outlets and arterial trunks in the human heart are exclusively based on histologically stained sections. So as to expand these studies, we performed immunohistochemical analyses of serially sectioned human embryos, along with three-dimensional reconstructions. The development of the cardiac arterial pole involves several parallel and independent processes of formation and fusion of outflow tract cushions, remodeling of the aortic sac and closure of an initial aortopulmonary foramen through formation of a transient aortopulmonary septum. Expression patterns of the transcription factors ISL1, SOX9 and AP2a show that, in addition to fusion of the SOX9-positive endocardial cushions, intrapericardial protrusion of pharyngeal mesenchyme derived from the neural crest contributes to the separation of the developing ascending aorta from the pulmonary trunk. The non-adjacent walls of the intrapericardial arterial trunks are formed through addition of ISL1-positive cells to the distal outflow tract, while the facing parts of the walls form from the protruding mesenchyme. The morphogenetic steps, along with the gene expression patterns reported in this study, are comparable to those observed in the mouse. They confirm the involvement of mesenchymal tissues derived from endocardium, mesoderm and migrating neural crest cells in the process of initial septation of the distal part of the outflow tract, and its subsequent separation into discrete intrapericardial arterial trunks. Key words: aortic arches; heart development; human embryo; outflow trac

Trabeculated Right Ventricular Free Wall in the Chicken Heart Forms by Ventricularization of the Myocardium Initially Forming the Outflow Tract

Recent molecular lineage analyses in mouse have demonstrated that the right ventricle is recruited from anterior mesoderm in later stages of cardiac development. This is in contrast to current views of development in the chicken heart, which suggest that the initial heart tube contains a subset of right ventricular precursors. We investigated the fate of the outflow tract myocardium using immunofluorescent staining of the myocardium, and lineage tracer, as well as cell death experiments. These analyses showed that the outflow tract is initially myocardial in its entirety, increasing in length up to HH24. The outflow tract myocardium, subsequently, shortens as a result of ventricularization, contributing to the trabeculated free wall, as well as the infundibulum, of the right ventricle. During this shortening, the overall length of the outflow tract is maintained because of the formation of a nonmyocardial portion between the distal myocardial border and the pericardial reflections. Cell death and transdifferentiation were found to play a more limited contribution to the initial shortening than is generally appreciated, if they play any part at all. Cell death, nonetheless, plays an important role in the disappearance of the myocardial collar that continues to invest the aorta and pulmonary trunk around HH30, and in the separation of the intrapericardial arterial vessels. Taken together, we show, as opposed to some current beliefs, the development of the arterial pole is similar in mammals and bird