SPECIFICATION OF THE BODY AXES AND THE BODY PLAN

Embryos may be thought of as being constructed with three orthogonal spatial axes (cephalocaudal, dorsoventral and laterolateral), plus a temporal axis. In mammalian embryos, axes cannot be specified at very early stages: embryonic axes can be defined only after the early extraembryonic structures have been formed and the inner cell mass can be seen. The position of the future epiblast can be predicted in human embryos when the hollow blastocyst has formed. The inner cell mass becomes (seemingly) randomly located on the inside of the trophectoderm and forms a population of epiblast cells subjacent to the trophoblast. This region implants first. It is not known whether the trophectoderm in contact with the inner cell mass initiates implantation, so that the future dorsal surface of the embryo is closest to the disrupted maternal vessels at the implantation site, or whether the inner cell mass can travel around the inside of the trophoblast to gain a position subjacent to the implantation site once implantation has started.

Axes may be conferred on the whole embryonic disc, which is initially flat and mainly two-dimensional. However, their subsequent orientation in the folded three-dimensional embryo will be completely different. The dorsal structures of the folded embryo form from a circumscribed central ellipse of the early flat embryonic disc (see Fig. 10.5). Lateral and ventral structures form from the remainder of the disc, and the peripheral edge of the disc eventually becomes constricted at the umbilicus (see Figs 10.9 and 10.10). Although the appearance of part of the epiblast is taken to specify the dorsal surface of the embryo, the inner layer, i.e. the hypoblast, is not by default a ventral embryonic structure.

The primary, cephalocaudal, axis is conferred by the appearance of the primitive streak in the bilaminar disc. The primitive streak patterns cells during ingression, and so also specifies the dorsoventral axis which becomes apparent after embryonic folding. The position of ingression through the streak confers axial, medial or lateral characteristics on the forming mesenchyme cells. The axial and medial populations remain as dorsal structures in the folded embryo, and the surface ectoderm above them will exhibit dorsal characteristics. The lateral plate mesenchyme will assume lateral and ventral positions after embryonic folding, and the surface ectoderm above this population will gain ventral characteristics.

The third and last spatial axis is the bilateral, or laterolateral axis, which appears as a consequence of the development of the former two axes. Initially, the right and left halves of the embryonic body are bilaterally symmetric. Lateral projections, the upper and lower limbs, develop in two places on each side of the body wall (somatopleure).

With the last axis established, the temporal modification of the original embryonic axes can be seen. The segmental arrangement of the cephalocaudal axis is very obvious in the early embryo and is retained in many structures in adult life. Similarly, dorsal embryonic structures remain dorsal and undergo relatively little change. However, structures that were originally midline and ventral, especially those derived from splanchnopleuric mesenchyme, e.g. the cardiovascular system and the gut, are subject to extensive shifts, and change from a bilaterally symmetric arrangement to an entire body that is now chiral, i.e. has distinct left and right sides.

The development of all the body organs and systems, organogenesis, begins after the dramatic events of gastrulation, when the embryo has attained a recognizable body plan. In human embryos this corresponds to the end of stage 10 (Fig. 12.1). The head and tail folds are well formed, with enclosure of the foregut and hindgut (proenteron and metenteron), although the midgut (mesenteron) is only partly constricted from the yolk sac. The forebrain projection dominates the cranial end of the embryo, and the buccopharyngeal membrane and cardiac prominence are caudal and ventral to it. The cardiac prominence contains the transmedian pericardial cavity, which communicates dorsocaudally with right and left pericardioperitoneal canals. These pass dorsally to the transverse septum mesenchyme and open caudally into the extraembryonic coelom on each side of the midgut. The intraembryonic mesenchyme has begun to differentiate and the paraxial mesenchyme is being segmented into somites. Neural groove closure is progressing caudally, so that a neural tube is forming between the newly segmenting somites. Rostrally, the early brain regions, which have not yet fused, can be discerned. The neuroepithelium is separated from the dorsal aspect of the gut by the notochord. The earliest blood vessels have appeared, and a primitive tubular heart occupies the pericardium. The chorionic circulation is soon to be established, after which the embryo rapidly becomes completely dependent upon the maternal bloodstream for its requirements. The embryo is connected to the developing placenta by a mesenchymal connecting stalk in which the umbilical vessels develop, and which also contains the allantois, a hindgut diverticulum. The lateral body walls are still widely separated. The embryo has contact with three different vesicles: the amnion, which is in contact with the surface ectoderm; the yolk sac, which is in contact with the endoderm; and the chorionic cavity, containing the extraembryonic coelom, which is in contact with the intraembryonic coelomic lining (see Fig. 10.10).

Fig. 12.1 A, Embryo at stage 11, showing the position of the intraembryonic coelom (contained by the walls coloured blue). B, The three major epithelial populations within a stage 11 embryo, viewed from a ventrolateral position. The neural tube lies dorsal to the gut; ventrally, the intraembryonic coelom crosses the midline at the level of the foregut and hindgut, but is lateral to the midgut and a portion of the foregut.

The early body plan of the embryo is segmented. The boundaries between the segments are maintained by the differential expression of genes and proteins that restrict cell migration in these regions. Organogenetic processes either retain the segmental plan, e.g. spinal nerves, or replace it locally, e.g. the modifications of somatic intersegmental vessels by the development of longitudinal anastomoses. Abnormalities may result from improper specification of segments along the cephalocaudal axis and may fail to produce the appropriately modified segmental plan.

The degree to which vertebrate embryos are developmentally constrained at this period of development is controversial. Comparative studies on the timing at which specific embryonic structures appear, heterochrony, have shown that other embryonic species do not follow the same developmental sequence as humans (Richardson & Keuck 2002). Although some developmental mechanisms are highly conserved, e.g. the homeobox gene codes, others may have been dissociated and modified in different vertebrate species during evolution.

Organogenesis, the further development of body regions and organs that is described elsewhere in this book, starts from about stage 10 (approximately 28 days). Although it is both conventional and convenient to consider the further development of each body system on an individual basis, not only do all systems develop simultaneously, they also interact and modify each other as they develop. This necessary interdependence is supported by the evidence of experimental embryology and reinforced by the phenomena of growth anomalies, which cut across the artificial boundaries of systems in most instances. For these reasons, it is recommended that the development of an individual system or body region should be studied in relation to others, especially those most closely associated with it, whether spatiotemporally or causally.

EMBRYONIC CELL POPULATIONS AT THE START OF ORGANOGENESIS

The developmental processes operating in the embryo between stages 5 and 9 enabled the construction of the bi- and tri-laminar embryonic disc, the intraembryonic coelom and new proliferative epithelia. From the end of stage 10, a range of local epithelial and mesenchymal populations now interact to produce viscera and appendages. The inductive influences on these tissues and their repertoire of responses are very different from those seen at the onset of gastrulation. The range of tissues present at the start of organogenesis, when the body plan is clear, is given below and shown in Figs 12.1 and 12.2. For a summary of the fates of the embryonic cell populations, see Fig. 12.3.

Fig. 12.2 A, Mesoblast populations within the early embryonic disc. B, Stage 11 embryo, showing the position of the intraembryonic coelom (contained by the walls coloured blue) and the positions of the sections (i)–(iv), which are shown in C. C, Transverse sections, arranged cranial to caudal, from a stage 11 embryo. The populations of mesenchyme and the sites of mesenchymal proliferation are indicated.

Fig. 12.3 Structures that will be derived from specific epithelial and mesenchymal populations in the early embryo. CNS, central nervous system.