FOLDING OF
THE EMBRYO
• In this lecture we shall concentrate on
those events which transform the
trilaminar embryo into a
• “tube within a tube”, segregating the
embryo from extraembryonic tissue except
at the umbilicus.
• These processes will also rotate the
developing heart tube into its thoracic
position.
• Finally, we shall examine how the coelom
is divided into the pleural, peritoneal and
pericardial cavities.
Learning objectives
• 1. To understand how the embryo is
segregated from the extra-embryonic
tissues with the exception of the umbilical
cord.
• 2. To understand the process whereby the
gut tube is formed and is lined with
endoderm.
• 3. To understand the events that result in
the incorporation of the extra-embryonic
coelom into the embryo, thereby forming
the peritoneal, pericardial and pleural
cavities.
• 4. To understand the role of cranial-caudal
flexion in the repositioning of the
buccopharyngeal membrane (future
opening of the mouth), heart tubes,
primitive pericardial cavity and a wedge of
mesoderm (septum transversum) which
will initiate diaphragm formation.
• At the same time the cloacal membrane
(future opening of gut and urinary tract) is
also brought into a ventral position.
• 5. To understand how the diaphragm is
formed.
• At the end of the third week, the germ disc
begins to overgrow the yolk sac,
ballooning into a convex shape, with the
peripheral areas of the germ disc
becoming the ventral surface of the
embryo.
• During 4th week a significant event in
the establishment of body-form is
folding.
• Folding converts flat trilaminar
embryonic disc into a cylindrical
embryo.
• Folding occurs in both longitudinal
and transverse planes.
• The longitudinal and transverse
foldings occur simultaneously.
• Concurrently, there is relative constriction
at the junction of embryo and yolk sac.
• Folding is due to rapid growth of central
nervous system and somites.
• The growth rate at the sides of the
embryonic disc fails to keep pace with the
rate of growth in the long axis as the
embryo increases rapidly in length.
• Developing embryo during 4th week
• Longitudinal and Transverse foldings are
in process
Longitudinal Folding
• Mainly due to rapid growth of
neural tube.
• Ends of the trilaminar germ disc
folds ventrally and produce head
and tail folds.
• Beginning of fourth week, neural tube
in cranial region grows very rapidly. It
thickens to form the primordium of the
brain.
• As the embryo grows the head region
projects over the prochordal plate or
buccopharyngeal membrane (future
site of stomodeum).
• Folding of the caudal end of the
embryo results primarily from the
growth of distal part of neural tube –
the primordium of spinal cord.
• As the embryo grows the tail region
projects over the cloacal membrane
(future site of the anus).
• Initially, (day 18) the developing brain projects dorsally
into the amniotic cavity.
• Prochordal plate is anterior to the developing neural
tube and cloacal plate is posterior to the neural tube.
• The connecting stalk along with allantois is posterior to
cloacal membrane.
• Developing heart tube is inferior to pericardial cavity.
• Septum transversum is anterior to pericardial cavity.
• Later (day 22) the developing forebrain grows cranially
beyond buccopharyngeal membrane and overhangs
developing heart.
• Concomitantly, the septum transversum (transverse
mesodermal septum), primordial heart, pericardial
cavity, and buccopharyngeal or oropharyngeal
membrane move onto ventral surface of the embryo.
• A small foregut and hindgut has developed.
• Buccopharyngeal membrane is vertical (ectoderm is
anterior, endoderm is posterior). Pericardial cavity is
now inferior to heart tube. Septum transversum is
posterior to heart tube and pericardial cavity.
• Cloacal membrane is vertical. Connecting stalk and
allantois has gone inferior to hindgut but they are
directed posteriorly.
• Day 25. Now the buccopharyngeal/oropharyngeal
membrane and cloacal membrane have completed
180 degree turns (ectoderm is inferior and endoderm
is superior). Note that the rotation is more in tail fold
than head fold.
• Foregut and hindgut have elongated.
• The connecting stalk and allantois are now directed
(project) inferiorly/ventrally.
• The constriction of yolk sac is now obvious.
• Day 28. Oropharyngeal and cloacal membranes have
rotated more and now facing each other.
• The yolk sac has further constricted. Midgut is now
clear but still connected to yolk sac through narrow
canal called vitelline duct.
• Connecting stalk along with allantois has gone nearer
to vitelline duct and associated splanchnic mesoderm.
• During longitudinal folding, part of the endoderm of the
yolk sac is incorporated into the embryo as the
foregut and hindgut.
• The foregut lies between the brain and heart.
Oropharyngeal membrane separates the foregut from
the stomodeum.
The terminal part of the hindgut soon dilates slightly to
form cloaca (primordium of urinary bladder & rectum).
• After folding, the septum transversum lies caudal to
the heart where it subsequently develops into the
central tendon of the diaphragm.
• Before folding, the primitive streak lies cranial to the
cloacal membrane; after folding, it lies caudal to it.
• After folding the connecting stalk and the vitelline duct
join each other and finally form umbilical cord.
• The folding also affects the arrangement of the
embryonic coelom (primordium of body cavities).
• Before folding, the coelom is a flattened, horseshoeshaped single continuous cavity.
• After folding, the coelom has become divided into
thoracic and abdominal cavity.
• Thoracic (pericardial) and abdominal (peritoneal)
cavities communicate each other through
pleuropericardial canals.
Transverse Folding
• The flat germinal disc also folds in
horizontal or transverse direction.
• Right and left lateral edges of
trilaminar germ disc not only grow
laterally but also move ventrally and
finally medially to meet in the midline.
• As the lateral edges of embryonic
disc grow they form right and left
lateral folds.
• Right and left lateral edges of trilaminar
germ disc grow
• laterally
• ventrally and
• finally medially to meet in the midline
• lateral edges form right and left lateral
folds.
• Transverse folding is produced by the
rapidly growing somites and neural
tube.
• The primordium of the ventrolateral
wall grows laterally, ventrally and
medially towards the median plane,
rolling the edges of the embryonic
disc and forming a roughly cylindrical
embryo.
• By the middle of 3rd week (day 17) a flat trilaminar
germinal disc has formed.
• Development of paraxial mesoderm and
formation of somites is mainly responsible
for transverse folding of embryo.
• As the paraxial mesoderm starts
developing the ectoderm is raised
bilaterally and neural groove forms
between these bilateral ridges.
• Paraxial mesoderm later forms somites.
The formation of somites and neural tube
further raises surface ectoderm dorsally.
• By the day-19 paraxial mesoderm has formed. The
neural groove is visible. The ectoderm shows bilateral
ridges. In the lateral plate of mesoderm small spaces
have started developing.
• Day-20. Somites have started forming. They are
thickening and raising folds of developing neural tube.
• Lateral plate mesoderm has become divided into
somatic and splanchnic mesoderms. Intra-embryonic
coelom has formed. It is communicating with extraembryonic coelom.
• Day-21. intra-embryonic coelom is well developed
now. The somites are more thickened. The embryo is
assuming a globular form.
• Day-22. Somites have further enlarged. Neural tube
has formed. Intra-embryonic coelom is wide. The yolk
sac is decreasing in size. Embryo is more globular in
shape.
Day-25.
The blue amnion is almost
surrounding the developing
embryo.
The yellow yolk sac is
constricted and going to be
divided into intra-embryonic
and extra-embryonic parts.
Initially, there is a wide
connection between the
midgut and yolk sac but after lateral folding the
connection is reduced to a yolk stalk.
Intra-embryonic coelom and extra-embryonic coeloms
still communicating.
• Day-28. The right and left growing edges of amnion
have merged with each other. The right and left edges
of surface ectoderm and parietal mesoderm have
joined each other. Intra-embryonic coelom is now
within the body of embryo.
• As the abdominal walls form, part of the endoderm
germ layer is incorporated into the embryo as the
midgut. Midgut is suspended to the dorsal body wall
by dorsal mesentery.
• As a result of longitudinal and transverse folding the
area of attachment of the amnion to the ventral
surface of the embryo is reduced to a relatively narrow
umbilical region. Connecting stalk and vitelline duct
join and form umbilical cord. The amnion surrounds
the umbilical cord from all sides.
• As the lateral folds and longitudinal folds fuse
ventrally and umbilical cord forms, the
communication between the intraembryonic and
extraembryonic coelomic cavities is reduced.
• As the amniotic cavity expands it obliterates
most of the extraembryonic coelom.
• The amnion forms the epithelial covering of the
umbilical cord.
• Body folding abnormalities are uncommon.
Fourth Week
• Major changes in body form occur
during the fourth week.
• At the beginning, the embryo (2.0 to
3.5 mm long) is almost straight and
has 9 pairs of somites that produce
conspicuous surface elevations.
• The neural tube is formed between right
and left chains of somites.
• Pharyngeal (branchial) arches are visible.
• The embryo is now slightly curved
because of the head and tail folds.
• The heart produces a large ventral
prominence and pumps blood.
Fourth Week
• Forebrain produces a prominent elevation of
head, and folding of embryo has given embryo
characteristic C-shaped curvature. A long,
curved tail is present.
• Upper limb buds become recognizable by day
26 or 27 as small swellings on the ventrolateral
body walls.
• Otic pits, primordial of internal ears, are also
visible.
• Lens placodes are visible on the sides of the
head.
• The fourth pair of pharyngeal arches and the
lower limb buds are visible by the end of the
fourth week.
• End of fourth week, an attenuated tail is a
characteristic feature.
• Rudiments of many of the organ systems,
especially the cardiovascular system, are
established.
• End of fourth week caudal neuropore is closed.