This document provides an outline for a lecture on general embryology. It covers topics like erythropoiesis, gastrulation, formation of the three germ layers, neurulation, somite formation, and differentiation of the mesoderm and endoderm. During gastrulation, cells migrate through the primitive streak to form the ectoderm, mesoderm and endoderm layers. The notochord forms in the midline and guides development. Neurulation involves the formation of the neural plate and tube which will become the central nervous system. Somites form from the paraxial mesoderm and differentiate into sclerotome, myotome and dermatome. The intermediate and lateral plate mes

1. General Embryology
Part 3
Embryology SCT for 1st year General Medicine.
Jón Kolbeinn Guðmundsson

2. Topic list
1. Erythropoesis.
2. Thrombopoeisis, monocytopoeisis and lymphocytopoeisis.
3. Granulocytopoeisis.
4. Spermatogenesis.
5. Oogenesis.
6. Fertilization and cleavage.
7. Formation of the blastocyst and bilaminar germ disc.
8. Formation and differentiation of the extraembryonic mesoderm.
9. Implantation. Formation and differentiation of the trophoblast. Early phases of
placentation.
10. Gastrulation, early differentiation of the intraembryonic mesoderm. (continued)
11. Differentiation of the intraembryonic mesoderm.
12. Differentiation of the ectoderm
13. Differentiation of the endoderm, folding of the embryo.
14. Fetal membranes. Umbilical cord. Amniotic fluid.
15. Development of the external features of the fetus. External features of a matured
newborn. Twin pregnancy. Fetal membranes in twins.
16. Development of the skull and the vertebral column.

3. Gastrulation, early
differentiation of the
intraembryonic
mesoderm
(continued)
Topic 10

4. A little review from last time.
In the 3rd week of development:
3 layers form  ectoderm, mesoderm, endoderm

5. Imagine now that we cut the top of the amniotic sac.
What you would see if you would look inside the sac
from above is the picture to the right ---->
It is the epiblast seen from above.
In the 3rd week, buccopharyngeal membrane, primitive streak and primitive node start
forming on the epiblast.
The formation of the primitive streak is controlled by the expression of a factor called
nodal (growth factor). The primitive node is maintained by HNF-3β
Primitive
node
Primitive
streak
Buccopharyngeal
membrane

6. Review of gastrulation.
Epiblast cells migrate through the
primitive streak, some of them occupy
the middle and become mesoderm.
Some of the migrating epiblast push
away the hypoblast layer and create
the endoderm.
The epiblast layer is now called
ectoderm.
We have now established 3 germ layers:
ectoderm, mesoderm and endoderm.
Also known as the Trilaminar Germ Disc
This process is called Gastrulation.
Pictures to the right
show the bilaminar
germ disc along with
it's amniotic sac and
yolk sac in a cross
section.
endoderm
ectoderm
mesoderm

7. The migrating epiblast cells migrate towards the
primitive streak and invaginate into the space
between the epiblast and hypoblast.
This migration of cells is controlled by a factor called
FGF8. (Fibroblast Growth Factor 8)
These cells establish the intraembryonic mesoderm,
which is a term used to distinguish it from the
extraembryonic mesoderm.
These cells spread in all directions and eventually
make contact with the splanchnic extraembryonic
mesoderm which covers the amnion and yolk sac.
Splanchnic
extraembryonic
mesoderm
Intraembryonic
mesoderm

8. Cloacal
membrane
Buccopharyngeal
membrane
Sagittal cut
The prechordal plate forms at the cephalic end of the germ
disc.
This eventually becomes the buccopharyngeal membrane,
which in later development becomes the oral opening to the GI
tract.
The cloacal plate forms at the caudal end of the germ disc.
This eventually becomes the cloacal membrane. This area in
later development becomes the anal opening and indicates the
caudal end of the embryo.
The thing to be aware of is that mesoderm can’t be found at
the buccopharyngeal membrane and cloacal membrane.
You could think of the ectoderm and endoderm as being two
sheets of paper stapled together at both ends.
mesoderm

9. Formation of the notochord
At around the same time of
formation of the trilaminar germ
disc, some of the migrating
ectodermal cells start migrating
through the primitive streak
heading in the cephalic direction.
These cells stick together and do
not spread in the lateral direction
like the mesodermal cells.
These cells are called
prenotochordal cells.

10. Endoderm
The prenotochordal cells become intercalated
in the midline of the newly formed endoderm.
Notochordal plate is formed, which exists for
only a moment since it soon starts to form a
solid tube lodged in the midline between the
ectoderm and endoderm.
Notochordal plate
Notochordal
plate

11. The notochordal cells align in a cephalic-to- caudal
fashion. The notochordal process is found just
behind the prechordal mesoderm
Soon they start to intercalate and form a solid tube
of cells starting at the cephalic end and work their
way towards the caudal end.
At the place of the primitive pit where the
migrating epiblast cells invaginated
 A temporary communication between the
amniotic sac and yolk sac forms called the
neuroenteric canal.
A protrusion of the yolk sac starts forming
called the allantois, it is considered an
evolutionary remnant and serves no clear
purpose in human development.
Amniotic
sac
Yolk sac
Neuroenteric
canal
Prechordal
mesoderm
Notochordal
process
Allantois

12. endoderm
Definite
notochord
Soon enough, the notochordal cells of the notochordal plate
completely detach from the endoderm and form the definite
notochord.
Definite notochord
The notochord is a very important structure involved in
guiding the development of the other structures in its
proximity.
It has been called “The Organizer” along with the
primitive node and prechordal plate.

13. Formation of body axes (very important)
As we know the body has different configuration
and structures depending on where you look.
A newborn baby has : Head, arms and feet
Right side and left side
Front and back
For example:
What makes the liver stay on the right side and
the heart slightly to the left?
The placing of organs depends on establishing of
body axes, and many pathologies are associated
with these processes going wrong.
Left-Right axis
Cranio-caudal
axis (head to toe)
Dorso-ventral axis
(back to front)
BABY

14. Cranio-caudal axis
The cranio-caudal axis is basically the formation of a
head region (cranial/cephalic) and tail region (caudal).
During gastrulation, some epiblast cells migrate towards
the cranial part of the bilaminar germ disc forming the
anterior visceral endoderm (AVE).
The AVE cells express certain genes (OTX2, LIM1, HESX)
and secretes factors called cerberus and LEFTY 1
These factors inhibit nodal activity (responsible for
primitive streak formation and maintenance) making
the cranial region.
Therefore there wont be any streak found on the
epiblast in the cranial area.

15. Left-Right axis
Many organs are asymmetrically placed in the
body, such as: heart, lung, gut, spleen, liver, etc.
1. FGF8 is secreted by cells in the primitive
streak.
1. This causes expression of nodal
2. Nodal expression is then restricted to the left
side of the embryo due to accumulation of
serotonin
3. The high concentration of serotonin causes
expression of MAD3 which restricts nodal
expression to left side.
4. Genes from the midline (notochord) called
SHH, LEFTY 1 and ZIC3, prevent nodal
expression from crossing over to the right
side.
6. Ultimately nodal acts on the lateral plate mesoderm on
the left side causing LEFTY 2 to upregulate PITX2
7. PITX 2 establishes left-sidedness
If establishment of the
left-right axis doen’t occur
we get what is called
laterality defect

16. Differentiation of the ectoderm
Topic 12

17. In the 3rd week, gastrulation is followed by another very important development.
Neurulation = formation of the neural tube
The neural tube is the structure which will eventually becomes our Central Nervous
System (brain & spinal cord)
Neural crest cells are also formed and become our Peripheral Nervous System

18. Neurulation
16 days
18 days
Primitive node and streak are
visible.
Ectoderm has a rather
elongated oval shape.

19. Molecular control of neurulation
BMP 4 is present throughout the ectoderm and the
mesoderm during gastrulation.
BMP 4 causes
Ectoderm to become
epidermis (skin layer)
Mesoderm to become
intermediate and lateral plate
mesoderm
If BMP 4 is inhibited in a certain part of
the ectoderm, then that area will by
default develop into NEUROECTODERM
(neural tissue)
in the cranial region
Noggin, chordin and follistatin inhibit BMP4
 Resulting in induction of forebrain and midbrain
In the caudal region
WNT-3a, FGF and Retinoic acid
 Eventually result in induction of hindbrain and
spinal cord
Cranial region Caudal region
Spinal cordhindbrainmidbrainforebrain

20. Upregulation of Fibroblast Growth Factor
(FGF) along with inhibition of BMP 4 by
noggin, chordin and follistatin.
What happens is that the notochord, prechordal
mesoderm and the primitive node release the
previously mentioned factors and organize the
formation of the neural tube and paraxial mesoderm
(in detail later)
This is why they have been called
“The organizers”
If these factors were to be absent for any reason, no
neural tube would form.
notochord

21. Neural plate
A thickened ectoderm starts
appearing, this is the neural plate.
19 days

22. 20 days 21 days
The neural plate lengthens along with the body
axis, while the lateral edges elevate and form
neural folds, the center also deepens to form
the neural groove
Neural fold
Neural groove
Soon the neural folds approach each other in the midline and fuse
together, starting around the 5th somite.
Somites are segments of paraxial mesoderm, visible on the outside
of the ectoderm (in more detail later)
Somite
Pericardial bulge
Otic placode
Somite
Fusion of
neural folds.

23. Anterior neuropore
Posterior neuropore
23 days
The fusion of the neural folds
continues cranially and caudally,
Before the tube closes completely we
have an Anterior neuropore and a
Posterior neuropore.
The anterior neuropore usually closes
around day 25
The posterior neuropore around day
28.

24. Clinical
Failure of the neural tube to close is
termed NEURAL TUBE DEFECT.
1. Failure of the anterior neuropore to
close will result in most of the brain not
forming, this is called anencephaly
(literally means “without brain”)
and it is usually not compatible with
life.*
2. Failure of the neural tube to close
anywhere from the cervical region
downwards (caudally) will result in spina
bifida.
Since neural tube closure happens in the end
of week 3, it is important for pregnant
women to have enough folic acid in their
blood during this time

25. Neural Crest Cells
Neural crest cells
Neural groove
Cells at the lateral border of the crest
of the neuroectoderm are called
neural crest cells.
These cells will dissociate from the
neural tube once it has formed and
undergo a transition from epithelial
cells to mesenchymal cells
These neural crest cells will migrate all
over the embryo and give rise to many
different cells which are listed on the
next slide.
Mesenchyme = connective tissue in the
embryo regardless of origin.
Surface
ectoderm

26. Schwann cells Glial cells
Sensory ganglia
neurons
Odontoblasts
Chromaffin cells
Melanocytes
Pharyngeal arch
cartilages
List of Neural crest derived
cells/structures
• Cranial and sensory ganglia
• Adrenal medulla
• Melanocytes
• Pharyngeal arch cartilages
(makes craniofacial skeleton)
• Head mesenchyme and
connective tissue
• Schwann cells
• Odontoblasts (formation of
teeth)
• Glial cells

27. Differentiation of
intraembryonic
mesoderm
topic 11

28. Eventually the mesoderm occupying the middle between
the ectoderm and endoderm will differentiate into 3 parts.
1. Paraxial Mesoderm
2. Intermediate Mesoderm
3. Lateral plate Mesoderm
Differentiation of intraembryonic mesoderm
Growth of the embryonic disc continues as more
epiblast cells migrate through the primitive streak
and make up mesoderm, the cephalic (head) part
grows faster than the caudal part.
Due to this, the primitive streak gradually
shortens towards the caudal end, however since
it stays at the caudal end of the epiblast, that
part is supplied by epiblast cells for a longer
period, giving it a slimmer shape.

29. Formation of Somites and Somitomeres
Somite (paraxial mesoderm)
Intermediate
mesoderm
Lateral plate
mesoderm
The formation of paraxial
mesoderm occurs by day 17 (3rd
week)
This part of the mesoderm will
eventually form somites and later
somitomeres.
Somite = mass of mesoderm
distributed along the two sides of the
neural tube.
Somitomere = loose mass of paraxial
derived cells. Form from the somite.

30. Somite differentiation
The differentiation of the
somite is influenced by what
factors are released from its
proximate surroundings.
The somite will differentiate into 3 basic things:
1. Sclerotome (light red) – becomes cartilage and bone
2. Myotome (red) – becomes muscle (2 parts)
3. Dermatome (pink) – becomes dermis of skin
Myotome
+
Noggin

31. The molecular players in somite differentiation.
Wnt and NT-3 (neurotropin) are both released
from the neural tube.
Wnt – acts on the dorsomedial part of the
somite cells to express Myf5. this makes it
differentiate into part of the myotome which
will give rise to back muscles. (epaxial)
NT-3 – acts on the middle portion of the somite
to express PAX3 which makes it into
dermotome.
Wnt + BMP 4 – the combination of Wnt from
the epidermis and the inhibiting effect of BMP 4
from lateral plate mesoderm causes the
dorsolateral portion of the somite to express the
muscle specific gene MyoD, this is the part of
the myotome which will give rise to body wall
and limb muscles. (hypaxial)
Back musclesBody wall &
limb muscles
Dermis of
skin

32. Sonic Hedge Hog (SHH) and Noggin are released
by the notochord and neural tube.
They induce expression of PAX1 on the
ventromedial part of the somite.
This causes it to differentiate into sclerotome,
which will eventually develop into bone and
cartilage.
Bone and
cartilage
Neural tube & notochord

33. Differentiation of Intermediate mesoderm and Lateral plate mesoderm
Intermediate mesoderm only
temporarily connects to the paraxial
mesoderm.
Later it differentiates into urogenital
structures:
• Nephrotomes
• Nephrogenic cord
• Gonads
• Urinary system
Intermediate Mesoderm
Lateral plate mesoderm is the part where
intraembryonic mesoderm and extraembryonic
mesoderm meet.
It forms 2 parts
Splanchnic/visceral
mesoderm (covering yolk
sac) will cover the gut tube
and become the mesentery
(serous membrane) –
Peritoneum, pericardium,
pleura.
Somatic/parietal
mesoderm (covering the
amnion). This will become
part of the amniotic sac.
Lateral plate mesoderm

34. Differentiation of the endoderm,
folding of the embryo.
Topic 13

35. Folding of the embryo
During neurulation, the neural plate folds in on itself to form the neural tube.
Almost simultaneously the lateral part of the ectoderm fold to the sides and the endoderm starts
folding into a tube.

36. Dorsal aorta
Dorsal
mesentery
Gut tube
Splanchnic (visceral)
mesoderm
Somatic (parietal)
mesodermAmniotic cavity
Intraembryonic
cavity

37. The embryo also folds cephalo-caudally – head fold & tail fold. Closure is due to lateral body wall folding and
cephalocaudal folding.
The gut tube is now divided into 3 different regions:
Foregut, Midgut and Hindgut

38. cloaca
Yolk sac
Buccopharyngeal
membrane
stomach
The midgut communicates with the
yolk sac via the vitelline duct
The buccopharyngeal membrane
marks the start of the foregut
The cloacal membrane marks the
end of the hindgut
Buccopharyngeal membrane ( mouth)
Cloacal membrane ( Anus)
Allantois
Vitelline duct
Cloacal
membrane

39. List of germ layer derivatives.
Ectoderm
Epidermis
Hair
Nails
Cutaneous glands
Mammary glands
Anterior pituitary gland
Internal ear
Enamel of teeth
Lens of eye
hypophysis
Mesoderm
Muscles
Bones
Dermis
Connective tissue
Urogenital system
Adrenal cortex
Cardiovascular system
Serous membranes
Endoderm
Epithelial linging of:
• GI tract
• Respiratory tract
• Urinary bladder
• Liver
• Pancreas
• Auditory tube
• Tympanic cavity
• Thyroid gland
Neuroectoderm
Central nervous system
Pineal body
Retina
Posterior pituitary gland

40. Questions
1. Define Gastrulation. PP
2. Name 3 structures that develop from the ectoderm during the 3rd week of embryogenesis. PP
3. Name 3 structures that develop from the neural crest. PP
The process of forming 3 primary germ layers (ectoderm,mesoderm,endoderm) from the epiblast involving
movement of cells through the primitive streak to form endoderm and mesoderm.
Neural tube, neuroectoderm, surface ectoderm
• Melanocytes
• Schwann cells
• Glial cells
• Cells of adrenal medulla

41. 4. Name 3 parts of the intraembryonic mesoderm at the beginning of its differentiation. PP
5. Name 3 clusters that derive from the somite. PP
6. Name the germ layer from which these develop. PP
a) Spinal cord
b) Epidermis of skin
c) Lens of eye
d) Hypophysis
e) Bone
f) Kidney
g) Blood
h) Epithelial components of lung
i) Thyroid gland
• Paraxial mesoderm
• Intermediate mesoderm
• Lateral plate mesoderm
• Sclerotome
• Myotome
• Dermatome
Ectoderm
Ectoderm
Ectoderm
Ectoderm
Mesoderm
Mesoderm
Mesoderm
Endoderm
Endoderm

42. 7. In the adult, what structure is derived from the notochord.
7. Name 4 factors released from cells that influence somite differentiation. PP
8. Name 5 molecules that have a role in the development of the body axis. PP
Noggin, chordin, follistatin, BMP 4, LEFTY 1
BMP 4, SHH, NT-3, Wnt
Nucleus pulposus, a component of the intervertebral disc.

43. a)
b)
c)
Notochord
Paraxial mesoderm
Yolk sac endoderm
10. Name the structures on the picture indicated by the arrows. PP

44. 11. From which germ disk does ______ develop?
a) Bone
b) Hypophysis
c) Thyroid gland
Mesoderm
Ectoderm
Endoderm
12. Define Neurulation. PP