2. 2
As per:
Competency based Undergraduate curriculum 1
• AN79.1 Describe the formation & fate of the primitive streak
• AN79.2 Describe formation & fate of notochord
• AN79.3 Describe the process of neurulation
• AN79.4 Describe the development of somites and intra-embryonic coelom
• AN79.5 Explain embryological basis of congenital malformations, nucleus
pulposus, sacrococcygeal teratomas, neural tube defects
• AN79.6 Describe the diagnosis of pregnancy in first trimester and role of
teratogens, alpha-fetoprotein
Continued in Chapter 8……….
Medical Council of India, Competency based Undergraduate curriculum for the Indian Medical Graduate,
2018. Vol. 1; pg 1-80.
3. 3
INTRODUCTION
Q. Enlist the major events of third week of gestation.
Third week of development begins after five weeks of the onset of last menstrual period.
Characteristics of third week of development:
1. Formation of primitive streak
2. Gastrulation: Formation of three germ layers
3. Formation of notochord
4. Formation of allantois
5. Formation of neural plate, neural tube and neural crest
6. Formation of somites
7. Formation of intra-embryonic coelom
8. Development of chorionic villi
5. Gastrulation
Formation of germ layers
• Q. Write a short note on gastrulation.
Definition
Process
Bilaminar embryonic disc → trilaminar disc
during the third week of development (Viva)
5
Formation of the primitive streak. (Day 16: Side view)
Formation of primitive streak. (Day 16: Top view)
6. 6
Figure 7.4: 15–16-day embryo: Gastrulation: Formation of
intra-embryonic mesoderm and definitive endoderm.
7. Steps
Day 15: Primitive streak appears that induces
gastrulation
Primitive streak: Thickened linear band of
epiblast in the midline of the dorsal part of the
embryonic disc.
Hensen’s node or primitive knot: Elevated
cranial end of primitive streak that surrounds a
depressed pit called primitive pit or blastopore.
Primitive groove: A narrow depressed central
area of primitive streak.
The epiblast cells migrate towards the
primitive streak. Migrating cells invaginate and
detach from primitive streak.
7
15–16-day embryo: Gastrulation: Formation of intraembryonic
mesoderm and definitive endoderm.
8. Invaginated cells
1. displace hypoblast cells to form embryonic
definitive endoderm.
2. form a layer between endoderm and epiblast
– known as intra-embryonic mesoderm.
Remaining cells (non-invaginating cells) of
epiblast form definitive ectoderm.
Thus, epiblast forms all three germ layers by
gastrulation. (Viva)
8
15–16-day embryo: Gastrulation: Formation of intraembryonic
mesoderm and definitive endoderm.
9. Migrating mesoderm separates ectoderm from
endoderm except at two places: cranially at
buccopharyngeal membrane and caudally at
cloacal membrane.
Buccopharyngeal membrane or oral
membrane:
It is a small oval depressed area at the cranial
end of the germ disc and it appears in the
prechordal plate.
In buccopharyngeal membrane, endodermal
cells are firmly adherent with the ectodermal
cells.
It is bilaminar, devoid of mesodermal cells.
It breaks down in the fourth week to form the
opening of the oral cavity. (MCQ)
9
Figure 7.5: Day 16: Germ disc
showing a path for the movement of
surface epiblast cells (white solid
arrows)
10. Cloacal membrane
- At the caudal end of the primitive streak,
germ disc remains bilaminar due to firm
endodermal attachment with ectoderm.
- Later, on further development, cloacal
membrane divides into anal and urogenital
membranes.
- The cloacal membrane disintegrates in the
seventh week to form the openings of the
anus and the urinary and genital tracts.
(MCQ)
Pericardial bar
- It is midline horseshoe-shaped
mesodermal cell condensation cranial to
the buccopharyngeal membrane.
10
Figure 7.5: Day 16: Germ disc
showing a path for the movement of
surface epiblast cells (white solid
arrows)
11. 11
Scanning electron micrograph 7.1#
: SEM showing three germ layers. A cut through
anterior end of embryo illustrates three germ layers: ectoderm, mesoderm and intraembryonic
endoderm. The mesoderm in ventral midline is notochordal plate. [Species: mouse, approximate
human age: 17 days, ventral view] Courtesy: Professor Kathleen Sulik
13. 13
Cellular basis of primitive streak formation
Koller's sickle or Rauber’s sickle:
Thickening of extraembryonic tissue at the caudal edge of the germ
disc.
Koller’s sickle induce adjacent epiblast to form primitive streak
by cell–cell interactions at the caudal end of embryonic disc.
Cellular basis of primitive streak formation involves four major
processes, namely,
1. Cell migration
2. Oriented cell division
3. Progressive delamination from epiblast
4. Convergent extension.
14. 14
Cellular basis of gastrulation
During gastrulation, cells undergo morphogenetic movements
as follows:
1. Epiboly: Spreading of an epithelial sheet
2. Emboly or internalisation: Movement of cells into the interior of an
embryo.
3. Convergence: Movement toward the midline
4. Extension: Lengthening in the cranial–caudal plane
Morphogenetic changes include changes in
1. Cell shape
2. Size
3. Position
4. Number
5. Cell-to-cell and cell-to-extracellular matrix adhesion.
15. 15
Cellular basis of gastrulation
Epithelial-to-mesenchymal transformation (EMT): It involves changes in
Cell-to-cell adhesion
Cell shape, cytoskeleton.
Snail gene (a zinc-finger transcription factor) expression
Repress epithelial characteristics in the mesenchymal cells.
Cease E-Cadherin (cell-to-cell adhesion molecule)
Induces expression of vimentin (cytoskeletal proteins) in mesodermal cells.
Establishing medial–lateral subdivisions of mesoderm
Dorsalising factors: Proteins of Noggin, Chordin, Nodal, Follistatin and Cerberus genes
Ventralising factors: Bmps and Wnts
Low Bmp and Wnt signaling dorsalises the mesoderm and induces notochord formation
High expression of Bmp and Wnt signaling ventralises mesoderm and form lateral plate
mesoderm.
16. 16
Some interesting facts
• Embryonic disc remains bilaminar at buccopharyngeal membrane (prechordal plate) and
cloacal membrane.
• Continuous migration of cells from primitive streak towards cranial region makes the disc
elongated craniocaudally.
• Cilia of cells of primitive node may be responsible for right–left visceral side determination. Its
abnormality may cause situs inversus (major visceral organs are reversed from their normal
positions).
• Primitive streak regresses by 26th
day of intrauterine life. (MCQ, Viva)
• During epithelial-to-mesenchymal transformation, epiblast cells often elongate, become flask
or bottle shaped, and develop pseudopodia (footlike processes), filopodia (thinner
processes) or lamellipodia (flattened processes), which allow them to migrate through the
primitive streak into the space between the epiblast and hypoblast.
17. 17
Notochord
Q: Write a short note on notochord
Definition
Notochord is a midline embryonic structure that develops during the
third week of development from the cells of primitive node.
Extent
From cranial end of primitive streak to the prechordal plate.
21. 21
Formation of notochord
Cells of the primitive knot proliferate.
Day 17th
-18th
day: Proliferated cells invaginate in between ectoderm up to the prechordal plate
to form solid cord called notochordal process or head process.
Cavity of primitive pit extend into notochordal process to form notochordal canal.
The cells of notochordal canal fuse with endoderm.
The cells of the notochord canal disappear in a craniocaudal direction and to form a
communication between amniotic cavity (via primitive pit) with yolk sac. This communication
is called neurenteric canal.
Neurenteric canal flattens to form notochordal plate in the roof of yolk sac.
Soon the flattening of the notochordal plate reverses by folding of notochordal plate.
The cells of notochordal plate get separated from endoderm to form solid cord of cells called
definitive notochord.
22. 22
Significance of notochord
Notochord is a characteristic feature of phylum Chordata animals.
Notochord defines the axis of the embryo and forms basis for the
developing axial skeleton specifically vertebral body.
In humans, notochord disappears except its remnants that in adult
represents nucleus pulposus of intravertebral discs.
24. 24
Importance of neurentric canal
Importance of neurentric canal
Neuroenteric canal provides nutrition from the yolk sac to rapidly
differentiating ectoderm as intra-embryonic blood circulation is not
developed during the third week of development. (MCQ, Viva)
25. 25
Role of e-cadherin and FGF8
E-cadherin is transmembrane protein that play role in epiblast cell
adhesion.
Fibroblast growth factor 8 (FGF8) is expressed by epiblast cells.
FGF8 acts as an ‘organiser’ and controls cell migration.
FGF8 inhibits e-cadherin production and thus, promotes cell
migration at the primitive streak and node.
Hence, primitive node is known as embryonic organiser or Spemann
organizer as it promotes formation of three germ layers (discovered
by Hans Spemann and Hilda Mangold in 1924). (MCQ)
26. 26
Sacrococcygeal teratoma
Primitive streak regresses at the end of third week of development and completely
disappears by the twenty-sixth day of development.
Cause
Persistent remnant of primitive streak
Features
It is the most common tumor in the new born (1 in 37,000 neonates).
It is usually non-malignant tumor.
As derived from primitive streak (pluripotent cells), tumor contains incompletely differentiated
derivatives of all the three germ layer, for example, hairs, bone, cartilage, muscles and so on.
Treatment
Surgical removal of tumor.
27. 27
Teratogenic agents
Teratogenic agents
Teratogenesis is the development of abnormality during germinal
period (1–3 weeks) or embryonic period (4–8 weeks) due to toxicity.
Teratogenic agent exposure (radiation, infection or rays) between
15th
–18th
day of development produce gross malformation.
28. 28
Allantois
Q: Write a short note on allantois.
Definition
Allantois or allanto–enteric diverticulum is an outpouching of yolk sac in
the connecting stalk.
Development and fate
Day 16: Outpouching of yolk sac in connecting stalk forms allantois.
On development of bladder, allantois forms urachus.
After birth, urachus forms median umbilical ligament.
29. 29
Allantois
Significance
In birds, reptiles and some mammals, allantois acts as a reservoir
of urine during embryonic life.
In human, blood vessels of allantois forms umbilical vessels.
Clinical aspects
Urachal cyst: It is the remnant of lining epithelium of the urachus.
Urachal sinus: It is the remnant of urachus that communicates
with the bladder or outside the body.
Urachal fistula: It is a persistent urachus that form the passage
from umbilicus to the urinary bladder.
30. 30
Some interesting facts
Holoprosencephaly
High alcohol consumption during period of gastrulation may result in
the holoprosencephaly.
It includes small forebrain, fused lateral ventricles, hypotelorism
(closely set eyes).
Sirenomelia/caudal dysgenesis
It is also known as mermaid syndrome.
Insufficient mesoderm in caudal portion of germ disc result in the
hypoplasia or fusion of lower limbs, anomalies of vertebrae, kidney
and genital organs and imperforated anus.
32. Development of chorionic villi
• Second week of gestation: Primary chorionic villi (inner
cytotrophoblast and outer syncytiotrophoblast) appears.
In the beginning of the third week, mesodermal cells penetrate in a
core of the primary villi to form secondary villi.
By the end of the third week, mesodermal cells differentiate to form
capillaries. Such villi with capillaries are called tertiary or definitive
chorionic villi.
Anchoring villus extends from the chorionic plate to decidua basalis.
Branches of anchoring villi forms free villi that floats in the
trophoblastic lacunar spaces.
Development of communication between capillaries of villi, chorionic
plate and connecting stalk and intra-embryonic vessels form
fetoplacental circulation.
The cytotrophoblast cells penetrate syncytiotrophoblast and form
outer cytotrophoblast shell that helps in the firm attachment with the
endometrial stroma.
32
33. 33
Fate of the germ layers
Fate of the germ layers
- Ectoderm give rise to epidermis, central and peripheral nervous
system and retina.
- Endoderm give rise to epithelial lining of respiratory tract,
gastrointestinal tract, glands opening in these tracts, pancreas, liver,
gallbladder.
- Mesoderm give rise to musculature, bone, cartilage, cardiovascular,
reproductive and excretory system.
37. Neurulation
• Q. Define neurulation and enlist the steps involved in
neurulation.
Definition
The process of formation of neural plate and neural folds
and closure of these folds to form neural tube is called
neurulation.
Process of neurulation
Formation of neural plate/medullary plate: At the
beginning of third week, the midline central part of the
ectoderm (in between primitive node and prechordal
plate) lying above the developing notochord thickens.
Elevation of edges of neural plate forms peripheral
neural folds and central depressed part forms neural
groove.
Elevation of neural folds continue and starts fusion in a
future cervical region and then extend in cranio–caudal
direction to form the neural tube. The conversion of the
neural plate into the neural tube is called neurulation. 37
38. Cranial and caudal neuropores are the open
ends of neural tube.
Day 25: Cranial neuropore closes
Day 27: Caudal neuropore closes (MCQ, Viva)
During the detachment of neural tube from
ectoderm, cells from the lateral margins of
neural plate/folds come to lie between neural
tube and ectoderm and these detached cells are
called neural crest cells. (MCQ, Viva)
Neural tube forms central nervous system and
neural crest forms peripheral and autonomic
nervous system.
Prior to the closer of the neuropores, amniotic
fluid circulates through the developing neural
tube to provide nutrition.
38
Neurulation
39. 39
Scanning electron micrograph 7.4#
: SEM showing neural folding with cranial and caudal neuropores.
The developing face is represented by the frontonasal region, and the first pharyngeal (branchial, visceral) arch.
[Species: mouse, approximate human age: 22 days, dorsolateral view].Courtesy: Professor Kathleen Sulik
41. Neural Crest
Q. Write short note on neural crest.
Definition
Lateral margins of neural plate at its
junction with rest of the ectoderm.
Process of formation
At the time separation of the neural tube from
the surface ectoderm, cells of neural crest also
get separated and come to lie between the
ectoderm and neural tube.
Neural crest cells further divide to form dorsal
mass and ventral mass.
41
43. 43
Clinical Embryology
Clinical image :
Holoprosencephaly (HPE).
A. Skull coverings are
dissected to show the
intact meninges.
B. Meninges are dissected
to expose brain –
holoprosencephaly.
(Image courtesy: Dr
Mamatha Gowda*).
45. 45
Further development
In the third week, neural tube formation begins and gets completed by
twenty-seventh day.
In the third week, mesodermal elements also differentiate to form paraxial
mesoderm, intermediate mesoderm and lateral plate mesoderm.
Intra-embryonic coelom appears in the mesoderm that divides lateral plate
mesoderm into two layers (somatopleuric and splanchnopleuric).
By the end of the, third week, folding of the embryo begins.
46. 46
Practice figure 7.1: Germ disc showing notochord,
primitive pit, primitive knot, primitive groove and cloacal
membrane.
Practice figure 7.2: Bilaminar germ disc showing
primitive knot and primitive streak.
![11
Scanning electron micrograph 7.1#
: SEM showing three germ layers. A cut through
anterior end of embryo illustrates three germ layers: ectoderm, mesoderm and intraembryonic
endoderm. The mesoderm in ventral midline is notochordal plate. [Species: mouse, approximate
human age: 17 days, ventral view] Courtesy: Professor Kathleen Sulik](https://image.slidesharecdn.com/chapter73rdwktslr-250320084416-0dc388a7/85/Chapter-7-3rd-wk-TSLR-POWER-POINT-PRESENTATION-11-320.jpg)
![39
Scanning electron micrograph 7.4#
: SEM showing neural folding with cranial and caudal neuropores.
The developing face is represented by the frontonasal region, and the first pharyngeal (branchial, visceral) arch.
[Species: mouse, approximate human age: 22 days, dorsolateral view].Courtesy: Professor Kathleen Sulik](https://image.slidesharecdn.com/chapter73rdwktslr-250320084416-0dc388a7/85/Chapter-7-3rd-wk-TSLR-POWER-POINT-PRESENTATION-39-320.jpg)
