Gastrulation
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.
Clinical relevance
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.
