The mesodermal tissues that give rise to the heart first become evident when the embryo is undergoing the process known as gastrulation. In the human, this occurs during the third week of development, while for the mouse, at a comparable stage of development, around seven days will have elapsed from fertilisation, and the embryo will be in the presomitic stage. The embryonic plate in humans, initially possessing two layers, is ovoid, and is formed at the union between the yolk sac and the amniotic cavity. In the midline of the long axis of the oval disc is found the primitive streak, with the node at its cranial end. Through this streak, cells migrate from the upper layer by the process called gastrulation to form the three germ layers of the embryo proper: the ectoderm, the endoderm, and the mesoderm. The mesoderm insinuates between the ectodermal and endodermal layers, which themselves are continuous with the amnion and yolk sac, respectively. Having insinuated, the mesoderm spreads laterally and cranially within the embryonic disc, ultimately giving rise to a variety of structures, such as the somites, which will produce the axial structures, and the lateral plate mesoderm, which will form the parietal body wall. The cells that are destined to form the heart are also derived from this mesodermal layer. They form a crescent virtually at the cranial border of the disc (fig 1). As this heart forming region achieves its crescentic shape, the central region of the ectoderm transforms into the neural plate. This folds to become the neural tube, with the developing brain at its cranial end. In the human, the developing heart is initially cranial within the disc relative to the neural folds.
Figure 1 Ventral views of mouse embryos having four, six, and eight somites, respectively (panels A–C), representing the period from 7 ½12 to 8 days after fertilisation, in which the myocardium has been labelled blue using a reporter transgene (more ...)
At this stage, the developing heart itself consists of a plate of promyocardial cells, intermingled with a plexus of endothelial strands, also derived from the cardiac crescent. The cardiac plate is positioned inferior to the presumptive pericardial cavity, which has arisen as a space within the mesoderm. With continuing folding of the disc, this heart forming region is moved into the developing neck of the embryo. The folding inverts the orientation of the developing heart relative to the neural structures and the gut. Initially the cardiac plate was inferior to the pericardial cavity but, subsequent to folding, it also folds into a tube between the pericardial space and the newly formed foregut that then becomes surrounded by the pericardial space. The process of folding is driven by the massive growth of the cranial end of the neural tube as it forms the brain, coupled with invagination of the endoderm to produce the foregut.
These events can now be visualised in animals such as the mouse, with the cardiac structures demonstrated by the genes and proteins they contain. The location of the promyocardial cells can be determined from the outset by the expression of NKX 2.5
, a master gene controlling cardiac development.1
The cells can be then be shown by staining for sarcomeric proteins as they acquire a myocardial phenotype, revealing their location within the cardiac crescent (fig 1). The arrangement is somewhat different in mouse compared to human, since the murine embryonic plate is cup-shaped rather than discoid, with the endoderm on the outside and the ectoderm on the inside of the cup.
Irrespective of the differences between species, the endothelial plexus, as described above, is formed at the same time within the cardiac region and within the embryo, ensuring the presence of a circulatory system. In the cardiac region, this creates the primary endocardial tube of the heart. The endocardial cells forming the tube come from both sides of the developing embryo and, as they form a lumen, are enveloped by myocardial cells, all this occurring within the newly formed pericardial cavity. The myocardium at this stage, however, does not completely surround the endothelial tube. Instead, it retains, in its dorsal aspect, continuity with the splanchnic mesoderm of the developing mediastinum, through the structure known as the dorsal mesocardium (fig 2).
Figure 2 This cross section is through the ventricular part of the heart tube of a mouse embryo with eight somites. At this stage, the tube is supported within the pericardial cavity by a mesocardium (arrows). The tissues have been incorporated with bromodeoxyuridine, (more ...)