Development of Gastrointestinal
Tract
We will take a very
short tour of early development prior to the trilaminar embryo stage, at which
time we will follow the development of the gastrointestinal tract in detail.
Thereafter, for each region of the gastrointestinal tract, we will begin with a
short summary of the specific embryology relevant to the structures in that
region. The single-celled zygote begins dividing roughly 30 hours after
an oocyte is fertilized by a spermatozoa. It continues dividing without growing
substantially until it reaches the 16-cell stage and is then referred to as a morula.
The morula consists of an outer cell mass surrounding an inner
cell mass, which will become the placenta and the embryo, respectively.
For the purpose of this section we will focus on the inner cell mass as it
morphs to create the body and the organs within.
As the zona pellucida (a protective covering of the oocyte and
later the zygote) gradually disappears, fluid penetrates the morula and creates
a space between the inner and outer cell masses. The inner cell mass remains in
contact with the outer cell mass in one section, which will eventually form the
connecting stalk and umbilical cord, connecting the embryo to the
placenta. The fluid- filled space between the two cell masses is called the blastocyst
cavity and at this time, roughly 4 days after fertilization, the entire
structure is called a blastocyst. Normally, the blastocyst implants into
the uterine lining starting on the sixth day and further development occurs
within.
On the eighth day, another fluid-filled space forms between the inner
cell mass and the rest of the blastocyst. This is the amniotic cavity;
despite its small initial size, it will eventually enlarge to surround the
entire embryo. The portion of the inner cell mass that is in contact with the
amniotic cavity, and amniotic fluid therein, is called the epiblast, and
the portion that is in contact with the blastocyst cavity is called the hypoblast.
The epiblast cells are tall columnar cells, and the smaller hypoblast cells
appear cuboidal or squamous (flat). The epiblast and hypoblast layers
constitute the bilaminar disc. By the ninth day, when the blastocyst has
fully implanted into the uterus, the blastocyst cavity is referred to as the primary
yolk sac. Cells that separate the primary yolk sac, bilaminar disc, and
amniotic cavity from the developing placenta (cytotrophoblast and syncytiotrophoblast)
form the extraembryonic mesoderm.
By the 12th day, fluid-filled gaps within the extraembryonic mesoderm
converge and form yet another space, the extraembryonic cavity, which
will compress the primary yolk sac before physically separating it and the
bilaminar disc from the rest of the developing placenta except for a connecting stalk that will eventually become the
umbilical cord. As the 13th and 14th days proceed, the primary yolk sac is
compressed and pinched in two by the expanding extraembryonic cavity. One small
remnant moves away from the bilaminar disc while the larger piece remains in
contact with the hypoblast and is now called the secondary yolk sac. The
secondary yolk sac is lined by cells that are derived from the hypoblast. In
one region, these hypoblast cells enlarge and form the prechordal plate, a structure that marks the cranial/
superior pole of the developing embryo. Opposite the prechordal plate, epiblast
cells begin to proliferate near the embryo’s caudal/inferior pole. These cells
will form a structure called the primitive streak. This will eventually
result in the process of gastrulation, during which the bilaminar disc
is replaced by a trilaminar disc. Gastrulation begins on the 15th day
and results in the replacement of the epiblast and hypoblast layers by three new germ cell layers, collectively
called the trilaminar embryo. It consists of the embryonic ectoderm,
embryonic mesoderm, and embryonic endoderm. As these layers are
referred to hereafter, the word “embryonic” will be dropped.
To form the trilaminar disc, the primary streak extends from the caudal
end of the epiblast toward the prechordal plate but does not quite reach it. As
it extends cranially, replicating epiblast cells involute into it, invading the
space between the epiblast and hypo- blast, creating a fissure called the primitive
groove. This process occurs along the entirety of the primitive streak, but
there are some important features that occur at its cranial end, at an area
called the primitive node. The epiblast cells that migrate through the
primitive node migrate between the epiblast and hypoblast layers, moving
directly toward the prechordal plate, forming a signaling structure called the notochordal
process, an important structure in directing further development of the
three germ cell layers. As gastrulation proceeds, the hypoblast is entirely
replaced by cells that migrate through the primitive streak and settle in
contact with the secondary yolk sac. This layer is the endoderm and will
produce many of the body’s glands as well as the cells that line the respiratory,
urogenital, and gastrointestinal tracts. The cells of the former epiblast are
now referred to as ectoderm; this layer will produce the epidermis, central
nervous system, peripheral ganglia, and other cells of neural crest derivation.
Between the endoderm and ectoderm is the mesoderm, a layer that will produce
the kidneys and gonads, as well as the vascular, muscular, and connective
tissue structures of the body. At this stage, we could choose to follow the
development of any of the organ systems, but for the purpose of this volume we
will focus on the development of the gastrointestinal system. Other systems
will be mentioned in a more cursory manner when their development affects the
gastrointestinal system.
The central region of the ectoderm pinches together to invade the
mesoderm and form the midline neural groove on the 14th day of
development. As development proceeds from the 16th to 18th day, the neural
groove pinches together and invades the mesoderm as the neural tube, which
differentiates to form the spinal cord, brainstem, and cerebral cortex. After
the neural tube has detached from the ectoderm, other ectodermal cells, called
the neural crest cells, migrate into the mesoderm. These cells migrate
throughout the developing mesoderm to form the sympathetic chain ganglia,
ganglia of the cranial nerves, and postsynaptic parasympathetic ganglia, among
others. The mesoderm also undergoes several changes: the paraxial mesoderm is found to the immediate left and right of
the neural tube and will form somites, which in turn form the axial skeleton,
musculature, and dermis. Just lateral to the par- axial mesoderm is the intermediate
mesoderm, which differentiates into gonads and precursors of the kidneys.
Lateral to the intermediate mesoderm is the lateral plate mesoderm, which
contributes to the body wall, limbs, and connective tissue structures that
anchor the organs within the body cavities. In the case of the digestive
system, the lateral plate mesoderm forms the abdominal wall that contains the contents of the peritoneal cavity but
it also forms the smooth muscle and connective tissues that surround and
support the gastrointestinal tract. It also creates the mesenteries that
connect the digestive organs to the anterior and posterior abdominal wall. As
mentioned already, the endoderm forms the lining of the gastrointestinal
tract and several of the organs that develop from it. We will now describe how
the trilaminar embryo morphs to create the abdominal cavity and organs within.
The lateral plate mesoderm is continuous on its lateral edge with the extraembryonic
mesoderm that surrounds the developing embryo. It is sandwiched by the
ectoderm and amniotic cavity dorsally; the endoderm and secondary yolk sac are
located ventral to it. At 14 days of development, the lateral plate mesoderm
constitutes a single mesodermal region, but shortly there-after, gaps form
within it that create a continuous, horseshoe-shaped space that extends from
right to left, going around the cranial end of the embryo. This space is the intraembryonic
cavity; as it enlarges, it becomes continuous with the extraembryonic
cavity and it splits the lateral plate mesoderm into two layers. The parietal
(somatic) layer of lateral plate mesoderm is the more superior of the two
and is in direct contact with the ectoderm and amniotic cavity. The more
inferior layer is the visceral (splanchnic) layer of lateral plate mesoderm and
is in contact with the underlying endoderm and secondary yolk sac. This
separation is complete but not really dramatic by the 16th day. However, as
this space enlarges, it pushes the visceral layer and endoderm medially,
creating a notable separation by the 18th day. The visceral layers of lateral
plate mesoderm and endoderm on each side grow closer to each other, pinching
the endoderm on the left and right, creating a tube that is separate from the
rest of the secondary yolk sac. As this proceeds, the yolk sac stretches away
from the developing gut tube and remains connected to it via the vitelline
duct at the midgut, which will form the small intestine and part of the
large intestine. Aside from its connection to the vitelline duct and secondary
yolk sac, the rest of the endoderm and accompanying visceral lateral plate
mesoderm fuse to form a complete tube that stretches from the oropharyngeal
membrane (developing mouth) to the cloacal membrane (eventual anus
and urogenital openings). This tube is the early gastrointestinal tract, and it
will give rise to all the organs of digestion
as well as the respiratory and urogenital tracts. From cranial to caudal, it is
divided into the foregut (esophagus, stomach, proximal duodenum, liver,
spleen, pancreas), midgut (distal duodenum, jejunum, ileum, vermiform
appendix, cecum, ascending and transverse colon), and hindgut (descending
colon, sigmoid colon, and rectum). In addition to the vitelline duct, another
pouch of endoderm stretches away from the developing gut tube, the allantois.
This pouch, originally a caudal extension
of the primary yolk sac, extends off of the developing hindgut, and as
development proceeds, it extends into the connecting stalk, cranial to the
cloacal membrane. It contributes to the wall of the urinary bladder, but that
is not our focus at this time. Eventually both the vitelline duct and allantois
will extend along-side each other into the umbilical cord, and aberrations of
each structure are associated with malformations of the midgut and urinary bladder, respectively.
While the gut tube is forming from the endoderm and visceral lateral
plate mesoderm, a similar process is occurring with the ectoderm and parietal
lateral plate mesoderm, so that a left and right lateral fold will form and
fuse anteriorly to become the body wall. The left and right lateral folds first
extend toward the yolk sac and then turn medially. As this happens, these layers
pull the amniotic sac, which had previously covered a small area, to surround
the entire developing embryo. Cross sections of the developing embryo at 18
days will appear remarkably different, depending upon whether or not the cross
section includes the secondary yolk sac and vitelline duct. A cross section
that includes the yolk sac will show an incompletely fused gut tube at the
midgut, with the vitelline duct leading away from, and opening into, a
ballooned yolk sac. The lateral folds have not yet migrated anteriorly enough
to form a complete body wall. However, a cross section in a more posterior
plane will exclude the yolk sac and show a fused anterior body wall surrounding
a circular gut tube. The gut tube remains anchored to the anterior body wall by
the ventral mesentery, which will largely disappear, and the dorsal mesentery,
which will remain and transmit the vessels and nerves that connect the gut tube
to the rest of the body. The gut tube, with its surrounding visceral layer of
lateral plate mesoderm, separates the right and left peritoneal cavities,
“descendants” of the intraembryonic coelom to either side. When the ventral
mesentery disappears, there will be a single peritoneal cavity. By this
time, the amniotic cavity almost entirely covers the developing embryo, with
only a narrow span of mesoderm separating the right and left lateral folds.
Before 1 month of development has passed, the heart has descended into
the thoracic region, bringing along a mesodermal structure, the septum
transversum, which will contribute to the diaphragm. The septum transversum
narrows the peritoneal cavity considerably, leaving two small openings between
the pericardial cavity in the thorax and the peritoneal cavity in the
abdomen. These are the pericardioperitoneal canals and they are normally
closed as the diaphragm receives a left and right pleuroperitoneal membrane from
the body wall. Contributions from the dorsal mesentery of the esophagus and
muscle from the body wall assist in closing these canals and creating the diaphragm by the ninth week.
Later, the musculature of the diaphragm develops as a secondary ingrowth from
the body wall. The phrenic innervation from the cervical spinal cord to the
diaphragm originates when the transverse septum first develops at the cervical
level of the embryo. As the septum shifts to a low thoracic level, the phrenic
nerves elongate. The commonest developmental abnormality of the diaphragm is a faulty growth of the left
pleuroperitoneal membrane, resulting in an opening through which abdominal
viscera may herniate into the left pleural cavity.
Caudal to the developing diaphragm is the foregut. The ventral and dorsal
mesenteries remain in contact with the foregut, but the ventral mesentery
disappears along the midgut and hindgut, leaving the developing gut tube
suspended in the abdominal cavity. From the dorsal aorta, the celiac trunk supplies
blood to the foregut, and its branches will supply all of the foregut organs as
they develop. Extensions of the foregut stretch into the ventral and dorsal
mesenteries to create the hepatic diverticulum and dorsal pancreatic
bud, respectively. The hepatic diverticulum will form the liver and
gallbladder but will also give rise to a ventral pancreatic bud, which
will fuse with the dorsal pancreatic bud to form the entire pancreas. The
ventral mesentery remains in contact with the developing liver, eventually
forming the falciform ligament. The further development of this region
will be covered in the sections related to the specific foregut organs, the
esophagus, stomach, duodenum, liver, gallbladder, and pancreas.
During the sixth week the midgut has begun to elongate substantially and
runs out of room within the peritoneal cavity. It moves into the umbilical
cord, creating a physiologic umbilical herniation, which is a normal
event in the development of the gastrointestinal system. The vitelline duct has
narrowed but still connects the midgut to the secondary yolk sac, and this
connection is one of the reasons that the physiologic herniation occurs,
pulling the midgut into the umbilical cord. The vitelline duct will typically
disappear roughly 10 weeks into development as the midgut starts returning to
the peritoneal cavity. The superior mesenteric artery is derived from
the vitelline artery and supplies all the developing midgut structures and,
eventually, all organs of the midgut. The further development of this region
will be covered in the sections related to the small and large intestines.
Development of the hindgut is intimately connected with the urinary and
reproductive systems. All three systems
initially empty into a common chamber, the cloaca, which is separated
from the amniotic cavity by a cloacal membrane. The allantois extends
from the cranial end of the cloaca and stretches into the umbilical cord
alongside the vitelline duct. Between 4 and 7 weeks, the mesoderm located between
the allantois and the vitelline duct/midgut, called the urorectal septum, extends
caudally and separates the hindgut from the rest of the cloaca, which will
hereafter be called the urogenital sinus. By the end of 7 weeks, the
urorectal septum has totally
partitioned the digestive and urogenital systems, leaving a urogenital
membrane and anal membrane on the external surface of the body in
the place of the cloacal membrane. The inferior mesenteric artery will
supply all the hindgut organs. The further development of this region will be
covered in the sections related to the large intestine and anal regions.
Although the foregut began as a simple, midline, tubular structure lined
by epithelium derived from endoderm, it twists, expands, and elongates to
create the adult relationships
between each abdominal organ. Fusing and expansion of the dorsal mesenteries
are key in this process. The portion of the foregut that will become the
stomach first starts to expand in the sagittal plane, ballooning outward on its
anterior and posterior surfaces. However, the expansion of the posterior
surface quickly outpaces the other side and the stomach begins to bend. The
enlarged expansion of the posterior side will become the stomach’s greater
curvature, and the anterior side will become the lesser curvature. As this is
happening, the presumptive stomach rotates so that the posterior side shifts
toward the left of the body while the anterior right side shifts to the right.
The rotation and expansion of the posterior side are what give the stomach its
characteristic shape, with the esophagus entering just to the right of the
fundus and greater curvature, and the outlet of the stomach, the pyloric
region, shifting to the right and slightly superior to the greater curvature.
This moves the stomach from a superior/inferior axis to more of a right/left
axis within the abdomen. The inner, circular layer of muscle at the terminus of
the stomach enlarges significantly to form the pyloric sphincter.
The rotation and expansion of the stomach do not occur in isolation. The
foregut is attached to the posterior body wall by a dorsal (posterior)
mesentery, called the dorsal mesogastrium, in which the spleen and
dorsal part of the pancreas will develop. The section of this mesentery between
the developing spleen and the stomach will become the greater omentum. Anteriorly
it is connected to the liver, and thereafter, to the anterior body wall by a ventral
(anterior) mesentery. The section of the ventral mesentery that attaches
the liver to the anterior body wall will become the falciform ligament, and
the section between the liver, stomach, and duodenum will form the lesser
omentum. As the stomach’s posterior surface expands and rotates to the
left, the attached mesentery follows, laying the spleen along the left side of
the abdominal cavity. The dorsal mesentery between the stomach and spleen
expands, folding onto itself and creating a large pocket between the two folds.
The pocket thus formed is called the omental bursa. Continued
rotation and expansion of the greater curvature bring this double-layered
“apron” to extend inferiorly from the stomach, falling anterior to the
transverse colon and small intestine. The motion of the developing stomach and
growth of the liver shift the stomach to the left and the liver to the right
side of the abdomen. This also brings the omental bursa to lie anterior to the
pancreas, inferior to the inferior surface of
the liver, and posterior to the stomach and lesser omentum, which can be
subdivided into the hepatogastric and hepatoduodenal ligaments. Occasionally
the omental bursa can extend superiorly and posteriorly to the liver as the superior
recess of the omental bursa. In its mature form, the omental bursa is
isolated from the rest of the abdominal cavity, except for a small opening
called the omental foramen located immediately posterior to the right
edge of the hepatoduodenal ligament.
