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Physiol. Rev. 83: 1223-1267, 2003; doi:10.1152/physrev.00006.2003
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Cardiac Chamber Formation: Development, Genes, and Evolution

ANTOON F. M. MOORMAN and VINCENT M. CHRISTOFFELS

Experimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Moorman, Antoon F. M., and Vincent M. Christoffels. Cardiac Chamber Formation: Development, Genes, and Evolution. Physiol Rev 83: 1223-1267, 2003; 10.1152/physrev.00006.2003.—Concepts of cardiac development have greatly influenced the description of the formation of the four-chambered vertebrate heart. Traditionally, the embryonic tubular heart is considered to be a composite of serially arranged segments representing adult cardiac compartments. Conversion of such a serial arrangement into the parallel arrangement of the mammalian heart is difficult to understand. Logical integration of the development of the cardiac conduction system into the serial concept has remained puzzling as well. Therefore, the current description needed reconsideration, and we decided to evaluate the essentialities of cardiac design, its evolutionary and embryonic development, and the molecular pathways recruited to make the four-chambered mammalian heart. The three principal notions taken into consideration are as follows. 1) Both the ancestor chordate heart and the embryonic tubular heart of higher vertebrates consist of poorly developed and poorly coupled "pacemaker-like" cardiac muscle cells with the highest pacemaker activity at the venous pole, causing unidirectional peristaltic contraction waves. 2) From this heart tube, ventricular chambers differentiate ventrally and atrial chambers dorsally. The developing chambers display high proliferative activity and consist of structurally well-developed and well-coupled muscle cells with low pacemaker activity, which permits fast conduction of the impulse and efficacious contraction. The forming chambers remain flanked by slowly proliferating pacemaker-like myocardium that is temporally prevented from differentiating into chamber myocardium. 3) The trabecular myocardium proliferates slowly, consists of structurally poorly developed, but well-coupled, cells and contributes to the ventricular conduction system. The atrial and ventricular chambers of the formed heart are activated and interconnected by derivatives of embryonic myocardium. The topographical arrangement of the distinct cardiac muscle cells in the forming heart explains the embryonic electrocardiogram (ECG), does not require the invention of nodes, and allows a logical transition from a peristaltic tubular heart to a synchronously contracting four-chambered heart. This view on the development of cardiac design unfolds fascinating possibilities for future research.


1 The conus arteriosus is considered a component part of the heart because it has a myocardial wall and lies within the pericardial cavity. It is a feature of the evolutionary primitive state. In amphibians it is called the bulbus cordis, a term that is also used for its equivalent in mammalian embryos. The more derived extant bony fish, like the zebrafish, do not have this cardiac compartment. They have a so-called bulbus arteriosus, which is not enclosed by cardiac muscle, but by elastic tissue and smooth muscle, and therefore is considered to be a specialization of the proximal part of the ventral aorta (256). However, similar to the mammalian condition (306, 326, 339), the bulbus arteriosus in zebrafish embryonic hearts is surrounded by myocardium that disappears with development (134, 135). The bony fish bulbus arteriosus might thus be homologous to the shark conus arteriosus and amphibian/mammalian bulbus cordis.

2 Reynolds number (Re) is a unitless number representative of the tendency of a liquid (or gas) to become turbulent. It is proportional to the velocity of flow and to the density, and inversely proportional to the viscosity.

Address for reprint requests and other correspondence: A. F. M. Moorman, Dept. of Anatomy & Embryology, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands (E-mails: a.f.moorman{at}amc.uva.nl; v.m.christoffels{at}amc.uva.nl).




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