If we consider the second week of development produces the bilaminar disc (Figure 14.1), we might say that the main event of the third week of development is the formation of the trilaminar disc. The process by which this takes place is called gastrulation.
The purpose of gastrulation is to produce the three germ layers from which embryonic structures will develop: ectoderm, mesoderm and endoderm.
Gastrulation is initiated at about day 14 or 15 with the formation of the primitive streak (Figure 14.2). The primitive streak runs as a depression on the epiblastic surface of the bilaminar disc and is restricted to the caudal half of the embryo. Towards the cephalic end there is a round mound of cells called the primitive node, surrounding the primitive pit.
The appearance of the primitive streak gives the observer an indication of the body axes that the cells are using to organise themselves. Until this point it was unclear which parts of the embryonic sheets were cephalic or caudal (superior or inferior in the adult), ventral or dorsal (anterior or posterior) and left or right.
With the primitive streak the embryologist can determine where the head and tail will develop, which side is the left side and which surface will form the outermost layers of the skin.
Epiblast cells migrate towards the streak and when they reach it they invaginate or slip under the epiblast layer to form new layers (Figure 14.3). The first cells to invaginate replace the hypoblast layer and produce the endodermal layer.
Some epiblast cells form the mesodermal layer between the epiblast layer and the endodermal layer. Cells migrating through the lateral part of the primitive node and cranial part of the streak become paraxial mesoderm, cells migrating through the mid‐streak level become intermediate mesoderm and cells that migrate through the caudal part of the streak are destined to be lateral plate mesoderm (see Chapter 25). Cells that migrate through the most caudal tip of the streak contribute to the extra‐embryonic mesoderm, along with the cells of the hypoblast.
The epiblast layer now becomes the ectodermal layer (Figure 14.4).
After cells have migrated through the streak and begun their path to specialisation, they continue to travel to different areas of the embryo. The first cells that travel towards the cephalic end form the prechordal plate, uccopharyngeal (or oropharyngeal) membrane.
The buccopharyngeal membrane will eventually become the mouth opening. Here there is no mesodermal layer; the ectoderm and endoderm are in direct contact. This also occurs at the cloacal membrane, which will become the opening of the anus.
This period of development is a good example of how the cells of the developing embryo are organised (see Chapter 3). Signalling molecules are a key part of this organisation. There are three groups of molecules involved in the control of our developing embryo: transcription factors, signalling molecules and cell adhesion molecules (CAMs).
Transcription factors act upon the cells that produce them and affect gene expression by binding DNA and controlling transcrip- tion of DNA to mRNA.
A signalling molecule secreted by a cell can affect other cells nearby or at a distance, or the cell that produces it. A cell must have an appropriate receptor ligand to be able to respond to a signalling molecule, and the affect may be positive (e.g. proliferation) or neg- ative (e.g. apoptosis). Signalling molecules are inducers of a wide range of cellular events. Growth factors are a well‐known group of signalling molecules.
CAMs allow cells to recognise similar cells or extracellular matrix structures, and aggregate. There are two main groups: calcium dependent (e.g. cadherins) and calcium independent (e.g. integrins). Often these three types of signalling work in combination to create the complex structures we see develop in morphogenesis. Cells of the primitive streak produce fibroblast growth factor 8 (a signalling molecule) and this molecule causes a down‐regulation in E‐cadherin (a CAM) production that usually make the cells sticky. Having less E‐cadherin means that the cells are more motile, thus stimulating migration towards the primitive streak.
Transcription factors brachyury (which acts more dorsally) and goosecoid (which activates chordin, a signalling molecule) are known to be involved in the differentiation of migrating cells from epiblast to mesoderm.
Also nodal, a signalling molecule of the transforming growth factor β (TGF‐β) family, is a mesoderm inducer and helps to maintain the primitive streak. An antagonist to nodal called cerberus is produced by cells of the hypoblast and thought to cause restriction of the streak at the caudal end of the embryo.
A range of factors are now in play, and the organisation of the embryo is becoming more complicated as it takes shape.
Gastrulation is a period of development very susceptible to teratogens. In week 3 of development (often before the mother knows of the pregnancy), factors that can have damaging effects on the embryo include alcohol, caffeine and tobacco. Other known factors that may affect cells at this stage include drugs such as thalidomide, temazepam, forms of retinoic acid (vitamin A), radiation, infections (e.g. rubella and herpes virus) and metabolic imbalances including folic acid deficiency and diabetes. If the embryo is exposed to these factors the upset to signalling or proliferation at an early stage in development results in defects that can be wide ranging and affect multiple developmental processes. Often, the defect originates from a lack of cell numbers in a certain region, and may be so catastrophic as to cause spontaneous abortion.
Sacrococcygeal teratomas occur when cells of the primitive streak get left behind in the sacrococcygeal region, and these cells develop into tumours. Often identified before birth with routine ult re external and can be removed surgically.