1. Third Week Development
Samara University
College of Health and Medical Sciences
Biomedical Department
By Dr. Awoll (MD)

2. Main events of the third week development
• Rapid development of the embryo from the embryonic disc during the
third week is characterized by
 Appearance of primitive streak
 Development of notochord
 Neurulation
 Differentiation of three germ layers
 Development of Somites
 Early development of cardiovascular system

3. Gastrulation
• Gastrulation is the process that establishes all three germ layers
(ectoderm, mesoderm, and endoderm) in the embryo
• Gastrulation begins with formation of the primitive streak on the
surface of the epiblast
• Initially, the streak is vaguely defined, but in a 15- to 16-day embryo, it
is clearly visible as a narrow groove with slightly bulging regions on
either side
• The primitive streak consists of the primitive groove, primitive node,
and primitive pit.
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4. Gastrulation…
• The cephalic end of the streak, the primitive node, consists of a
slightly elevated area surrounding the small primitive pit
• Cells of the epiblast migrate toward the primitive streak
• Upon arrival in the region of the streak, they become flask-shaped,
detach from the epiblast, and slip beneath it
• This inward movement is known as invagination
• Once the cells have invaginated, some displace the hypoblast, creating
the embryonic endoderm, and others come to lie between the epiblast
and newly created endoderm to form mesoderm
• Cells remaining in the epiblast then form ectoderm

5. Implantation site at the end of the second week
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6. Representative view of the germ disc at the end of the second week of development.
The amniotic cavity has been opened to permit a view on the dorsal side of the
epiblast.
The hypoblast and epiblast are in contact with each other and the primitive streak
forms a shallow groove in the caudal region of the embryo
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7. Dorsal aspect of an 18-day embryo.
The embryo has a pear-shaped appearance and shows the primitive streak
and node at its caudal end 7

8. Gastrulation…
 The primitive streak after giving rise to mesoderm, gradually
regresses and then disappears
• Thus, the epiblast, through the process of gastrulation, is the source of
all of the germ layers, and cells in these layers will give rise to all of
the tissues and organs in the embryo

9. A. Dorsal side of the germ disc from a 16-day embryo indicating the movement of surface
epiblast cells (solid black lines) through the primitive streak and node and the subsequent
migration of cells between the hypoblast and epiblast (broken lines).
B. Cross section through the cranial region of the streak at 15 days showing invagination
of epiblast cells. The first cells to move inward displace the hypoblast to create the
definitive endoderm. Once definitive endoderm is established, inwardly moving epiblast
forms mesoderm 9

10. Gastrulation…
• As more and more cells move between the epiblast and hypoblast layers,
they begin to spread laterally and cephalad
• Gradually, they migrate beyond the margin of the disc and establish contact
with the extraembryonic mesoderm covering the yolk sac and amnion
• In the cephalic direction, they pass on each side of the prechordal plate
• The prechordal plate forms between the tip of the notochord and the
buccopharyngeal membrane and is derived from some of the first cells
that migrate through the node in a cephalic direction
• Later, the prechordal plate will be important for induction of the
forebrain

11. Gastrulation …
• The cloacal membrane is the future site of the anus where the
epiblast and hypoblast cells fuse.
• The cloacal membrane is formed at the caudal end of the embryonic
disc
• This membrane, which is similar in structure to the buccopharyngeal
membrane, consists of tightly adherent ectoderm and endoderm cells
with no intervening mesoderm
• When the cloacal membrane appears, the posterior wall of the yolk
sac forms a small diverticulum that extends into the connecting stalk

12. Allantois
• This diverticulum, the allantoenteric diverticulum, or allantois,
appears around the 16th day of development
• Function
• Early blood formation
• Development of urinary bladder
• As bladder enlarges it changes in to urachus, median umbilical cord in
adult.
• Blood vessels of allantois become umbilical aa

13. A. Drawing of a sagittal section through a 17-day embryo.
The most cranial portion of the definitive notochord has formed,
while prenotochordal cells caudal to this region are intercalated into
the endoderm as the notochordal plate
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14. Gastrulation…
• The buccopharyngeal membrane at the cranial end of the disc
consists of a small region of tightly adherent ectoderm and endoderm
cells that represents the future opening of the oral cavity

15. Gastrulation

16. Notochord
 Cellular rod formed by transformation of notochordal process
 Naturally occurring inducers from the primitive streak region induces notochordal precursor
cells to form notochord
• Is a solid cylinder of mesoderm extending in the midline of the trilaminar embryonic disk
from the primitive node to the prochordal plate.
• It has a number of important functions, which include the following:
• The notochord induces the formation of the vertebral body of each of the vertebrae.
• The notochord degenerates as the bodies of the vertebrae form, but small portions of it
persist as the nucleus pulposus of each intervertebral disc.
• Define primordial axis of the embryo and gives its rigidity
• Serve as the base for the development of axial skeleton
• Primary inductor in early embryo that induces the overlying embryonic ectoderm to
thicken and form the neural plate

17. Formation of the Notochord
• Prenotochordal cells invaginating in the primitive pit move forward
cephalad until they reach the prechordal plate
• These prenotochordal cells become intercalated in the hypoblast so that,
for a short time, the midline of the embryo consists of two cell layers that
form the notochordal plate
• As the hypoblast is replaced by endoderm cells moving in at the streak,
cells of the notochordal plate proliferate and detach from the endoderm
• They then form a solid cord of cells, the definitive notochord, which
underlies the neural tube and serves as the basis for the axial skeleton
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18. Formation of the Notochord…
• Because these events occur in a cranial-to-caudal sequence, portions
of the definitive notochord are established in the head region first,
and caudal regions are added as the primitive streak assumes a more
caudal position
• The notochord and prenotochordal cells extend cranially to the
prechordal plate (an area just caudal to the buccopharyngeal
membrane) and caudally to the primitive pit
• At the point where the pit forms an indentation in the epiblast, the
neurenteric canal temporarily connects the amniotic and yolk sac
cavities

19. Notochord…
C. Schematic cross section through the
region of the notochordal plate.
Soon the notochordal plate will detach from
the endoderm to form the definitive
notochord.
E. Schematic view showing the
definitive notochord

20. Notochord…
 Some mesenchymal cells migrate cranially from the primitive node
and pit forming a median cellular cord, notochordal process
 It soon acquires a lumen, notochordal canal
 Grow until prechordal plate/ primordium of oropharyngeal
membrane/
 Some cells from the primitive streak migrate cranially on each side of
notochordal process and around the prechordal plate
 Meet cranially to form the cardiogenic mesoderm

21. Clinical correlates
• Remnants of Notochordal Tissue
• Both benign and malignant tumors (chordomas) may form from
vestigial remnants of notochordal tissue.
• Approximately one third of chordomas occur at the base of the
cranium and extend to the nasopharynx.
• Chordomas grow slowly and malignant forms infiltrate bone

22. Growth of the Embryonic Disc
• The embryonic disc, initially flat and almost round, gradually becomes
elongated, with a broad cephalic and a narrow caudal end
• Expansion of the embryonic disc occurs mainly in the cephalic region; the
region of the primitive streak remains more or less the same size
• Growth and elongation of the cephalic part of the disc are caused by a
continuous migration of cells from the primitive streak region in a
cephalic direction
• Invagination of surface cells in the primitive streak and their subsequent
migration forward and laterally continues until the end of the fourth week
• At that stage, the primitive streak shows regressive changes, rapidly
shrinks, and soon disappears
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23. Clinical Correlates
• Teratogenesis Associated With Gastrulation
• The beginning of the third week of development, when gastrulation is
initiated, is a highly sensitive stage for teratogenic insult
• At this time, fate maps can be made for various organ systems, such as
the eyes and brain, and these cell populations may be damaged by
teratogens
• For example, high doses of alcohol at this stage kill cells in the anterior
midline of the germ disc, producing a deficiency of the midline in
craniofacial structures and resulting in holoprosencephaly
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24. Clinical Correlates…
• In such a child, the forebrain is small, the two lateral ventricles often
merge into a single ventricle, and the eyes are close together
(hypotelorism)
• Because this stage is reached 2 weeks after fertilization, it is
approximately 4 weeks from the last menses.
• Therefore, the woman may not recognize she is pregnant, having
assumed that menstruation is late and will begin shortly
• Consequently, she may not take precautions she would normally
consider if she knew she was pregnant

25. Clinical Correlates…
• Gastrulation itself may be disrupted by genetic abnormalities and toxic
insults
• Caudal dysgenesis (sirenomelia)
• Insufficient mesoderm is formed in the caudal-most region of the
embryo
• Because this mesoderm contributes to formation of the lower limbs,
urogenital system (intermediate mesoderm), and lumbosacral
vertebrae, abnormalities in these structures ensue
• Affected individuals exhibit a variable range of defects, including
hypoplasia and fusion of the lower limbs, vertebral abnormalities,
renal agenesis, imperforate anus, and anomalies of the genital organs

26. Sirenomelia (caudal dysgenesis).
Loss of mesoderm in the lumbosacral region has resulted in fusion
of the limb buds and other defects. 26

27. Early development of CVS
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• At the beginning of 3rd week blood vessel formation begin in the
extraembryonic mesoderm of yolk sac, connecting stalk and chorion due
to
• Urgent need for blood vessels to bring oxygen and nourishment by
diffusion from extraembryonic coelom and yolk sac
• Primordial uteroplacental circulation begins.
• The formation of embryonic vascular system involves two process:
vasculogenesis and angiogenesis

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A. vasculogenesis and angiogenesis
1. Mesenchymal cells differentiate in to endothelial cell precursors
angioblasts cluster in to blood islands
2. Small cavities appear within the blood islands by confluence of
intercellular clefts
3. Angioblasts flattent to form endothelial cells that arrange themselves
around cavities in the blood islands to form endothelium
4. Endothelial lined cavities fuse to form networks of endothelial channels
/vasculogenesis/
5. Vessels sprout out in to adjacent areas by endothelial budding and fuse
with other vessels /angiogenesis/

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30. 30
B. Primordial CVS
• Heart and blood vessels arise from mesenchymal cells in the
cardiogenic area
 is a horseshoe-shaped region of mesoderm located at the cranial end
of the trilaminar embryonic disk rostral to the prochordal plate.
 This region forms the future heart
• Paired longitudinal endothelial lined channels- endocardial heart tubes
develop and fuse to form primordial heart tube
• Tubular heart join with blood vessels in the embryo, connecting stalk,
chorion, and yolk sac to form primordial CVS.
• 21st day blood circulation begin and heart begin to beat
• CVS is the 1st organ system to reach its functional state

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32. Further Development of the Trophoblast
• By the beginning of the third week, the trophoblast is characterized by
primary villi that consist of a cytotrophoblastic core covered by a
syncytial layer
• During further development, mesodermal cells penetrate the core of
primary villi and grow toward the decidua
• The newly formed structure is known as a secondary villus
• By the end of the third week, mesodermal cells in the core of the villus
begin to differentiate into blood cells and small blood vessels, forming
the villous capillary system
• The villus is now known as a tertiary villus or definitive placental
villus
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33. Development of a villus
A. Transverse section of a primary villus showing a core of cytotrophoblastic cells
covered by a layer of syncytium
B. Transverse section of a secondary villus with a core of mesoderm covered by a
single layer of cytotrophoblastic cells, which in turn is covered by syncytium
C. Teritiary villus, mesoderm of the villus showing a number of capillaries and
venules
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34. Further Development…
• Capillaries in tertiary villi make contact with capillaries developing in
mesoderm of the chorionic plate and in the connecting stalk
• These vessels, in turn, establish contact with the intraembryonic
circulatory system, connecting the placenta and the embryo
• Hence, when the heart begins to beat in the fourth week of
development, the villous system is ready to supply the embryo proper
with essential nutrients and oxygen

35. Further Development…
• Meanwhile, cytotrophoblastic cells in the villi penetrate progressively
into the overlying syncytium until they reach the maternal
endometrium
• Here they establish contact with similar extensions of neighboring
villous stems, forming a thin outer cytotrophoblast shell
• This shell gradually surrounds the trophoblast entirely and attaches the
chorionic sac firmly to the maternal endometrial tissue

36. Longitudinal section through a villus at the end of the third week of development.
Maternal vessels penetrate the cytotrophoblastic shell to enter intervillous spaces, which
surround the villi.
Capillaries in the villi are in contact with vessels in the chorionic plate and in the connecting
stalk, which in turn are connected to intraembryonic vessels.
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37. Further Development…
• Villi that extend from the chorionic plate to the decidua basalis (the
part of the endometrium where the placenta will form) are called stem
or anchoring villi
• Those that branch from the sides of stem villi are free (terminal) villi,
through which exchange of nutrients and other factors will occur
• The chorionic cavity, meanwhile, becomes larger, and by the 19th or
20th day, the embryo is attached to its trophoblastic shell by a narrow
connecting stalk
• The connecting stalk later develops into the umbilical cord, which
forms the connection between placenta and embryo

38. Presomite embryo and the trophoblast at the end of the third week.
Tertiary and secondary stem villi give the trophoblast a characteristic radial appearance.
Intervillous spaces, which are found throughout the trophoblast, are lined with syncytium.
Cytotrophoblastic cells surround the trophoblast entirely and are in direct contact with the
endometrium.
The embryo is suspended in the chorionic cavity by means of the connecting stalk
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39. Review question
1. The first indication of
gastrulation in the embryo is
A. formation of the primitive
streak
B. formation of the notochord
C. formation of the neural tube
D. formation of extraembryonic
mesoderm
E. formation of tertiary chorionic
villi
2. Which germ layers are present
at the end of week 3 of
development (day 21)?
A. Epiblast only
B. Epiblast and hypoblast
C. Ectoderm and endoderm
D. Ectoderm, mesoderm, and
endoderm
E. Epiblast, mesoderm, and
hypoblast

40. END OF THIRD WEEK DEVELOPMENT
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