The Third Week

• Gastrulation
• Neurulation
• Development of Somites
• Development of Intraembryonic Coelem
• Early Development of the Cardiovascular System
• Development of Chorionic villi
• Summary of the Third Week of Development
• Applied Embryology
• Rapid development of the embryo from the bilaminar germ disc in the
third week is characterized by:
• Appearance of the primitive streak
• Development of the notochord
• Differentiation of the three germ layers from which all embryonic
tissues and organs develop
• Estimation of the third week of embryonic development is during the
week following the first missed menstrual period
• This is 5 weeks after the onset of the last normal menstrual period
(LNMP)
• Missing a period or cessation of menstruation though often is the first
indication of possible pregnancy other causes of cessation must also
be considered. Such as severe stress
Clinical application:
The syncytiotrophoblast secretes human chorionic
gonadotrophin hormone which prevents the
degeneration of the corpus luteum. It also stimulates
the production of progesterone which in turn is
important in sustaining the placenta. By the end of the
2nd week, the amount of this hormone will be sufficient
to be detected in the maternal blood and urine. This is
the basis of pregnancy test.
• Early Pregnancy Factor (EPF) can detected 24 to 48 hours after
fertilization
• Bleeding at the site of implantation can occur – lacunar stage
• Leads to errors in determining expected dates of delivery or
confinement
• Nausea and vomiting may occur
 Gastrulation
• Definition: the process by which the bilaminar germ/embryonic disc is
converted into a trilaminar embryonic disc.
• Gastrulation is the beginning of morphogenesis
• This is most characteristic event occurring during the third week of
gestation
• Gastrulation begins with formation of the primitive streak on the
surface of the epiblast
• Each of these layers will give rise to all of the tissues and organs in the
embryo
The three germ layers

• Ectoderm forms the epidermis and the nervous system

• Endoderm gives rise to epithelium of the respiratory and digestive

tracts, glandular cells of the liver and pancreas

• Mesoderm is the source of blood cells and bone marrow, skeleton,

skeletal muscle, reproductive and excretory organs
Primitive streak
• At the beginning of the third week, an opacity is formed by a
thickened linear band of epiblast
• Appears caudally in the median plane of the dorsal aspect
• The primitive streak results from the proliferation and migration of
cells of the epiblast to the median plane
• 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 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
• 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.
• Prechordal plate
• Buccopharyngeal membrane
• Cardiogenic area
Fate Map Established During Gastrulation

• Regions of the epiblast that migrate and ingress through the primitive streak
have been mapped and their ultimate fates determined
• Cells that ingress through the cranial region of the node become notochord;
• those migrating at the lateral edges of the node and from the cranial end of
the streak become paraxial mesoderm;
• cells migrating through the midstreak region become intermediate
mesoderm;
• those migrating through the more caudal part of the streak form lateral plate
mesoderm; and cells migrating through the caudal-most part of the streak
contribute to extraembryonic mesoderm (the other source of this tissue is the
primitive yolk sac [hypoblast]
Fate of the primitive streak
• 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.
• Because elongation of the notochord is a dynamic process, the cranial
end forms 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
• When the cloacal membrane appears, the posterior wall of the yolk
sac forms a small diverticulum that extends into the connecting stalk.
• This diverticulum,the allantoenteric diverticulum,or allantois,appears
around the 16th day of development. Although in some lower
vertebrates the allantois serves as a reservoir for excretion products
of the renal system, in humans it remains rudimentary but may be
involved in abnormalities of bladder development
• This contributes to the urachus and forms the median umbilical
ligament
Neurulation
• Neurulation is the formation of the vertebrate nervous system in
embryos.
• The notochord induces the formation of the CNS by signaling the
ectoderm above it to form the thick and flat neural plate.
• The neural plate then folds in on itself to form the neural tube, which
will then later differentiate into the spinal cord and brain.
Neurulation (cont’d)
• Different portions of the neural tube then form by
2 different processes in different species:
1. Primary Neurulation – the neural plate creases
inward until the edges come into contact and then
fuse.
2. Secondary Neurulation – the tube forms by
hollowing out of the interior of a solid precursor
23-26 days of Human
Formation of the Neural Tube

• Secondary Neurulation
1. Occurs beyond the caudal neuropore
2. lumbar and tail region
3. Starts with formation of medullary cord
4. Cavitation of cord to form hollow tube
Neurulation
• The embryonic ectoderm over • By the end of week 3, the
the developing notochord neural folds move together,
thickens to form a neural plate fuse, and convert the neural
. plate into the neural tube.
• The ectoderm of the plate is • Closure begins in the middle of
called neuroectoderm and the embryo and progresses
eventually gives rise to the toward both cephalic and
central nervous system (brain caudal ends. It begins on day
and spinal cord). 21.
• Neuroectodermal cells at the • The anterior or cranial
lateral edge of the neural plate neuropore closes in week 4
-do not become part of the (day 24), whereas the
tube but form a neural crest posterior or caudal neuropore
over the neural tube and give closes near day 26.
rise to the neural crest cells.
40
Neural tube formation and neural crest
cells migration

42
23-26 days of Human
 The neural crest cells

11/14/2020 45
Differentiation of Brain Vesicles

• Anterior neural tube bulges: 3 primary vesicles:

• Then further differentiation into 5 secondary
vesicles:


DEVELOPMENT OF
SOMITES
• During notochord and neural tube formation the intraembryonic
mesoderm on each side proliferates to form a thick longitudinal
column.
• This is the paraxial mesoderm
• Each column is continuous laterally with other mesoderm-
intermediate mesoderm
• The intermediate mesoderm thins out laterally into the lateral
mesoderm
• Towards the end of the third week the paraxial mesoderm
differentiates and begins to divide into cuboidal bodies.
• These are the somites
• These blocks are located on each side of the developing neural tube
• About 38 pairs of somites form during the somite period of
development -20 to 30 day
• By end of the 5th week 42 to 44 pairs of somites are present
 Somites
• Form distinct surface elevation on the embryo
• Triangular in transverse section
• Has a transient unimportant slitelike cavity – myocoele
• Somites due to prominence are used as one criteria for determining
the embryo age
• The number of the somites that are found is used to determine the
embryo's age
• Somites first appear in the future occipital region of the embryo
• Develop craniocaudally and give rise to the axial skeleton and
musculature
Development of the intraembryonic coelom
• This the primordium of body cavity
• Small isolated spaces appear coelomic spaces or vesicle in the lateral
mesoderm and cardiogenic area
• The fuse or coalesce to form a single horse shoe-shaped cavity
• Intraembryonic coelom
• This divides the lateral mesoderm into two layers
• Somatic/parietal layer continuous with the extraembryonic
mesoderm covering the amnion
• Splanchnic or visceral layer continuous with the extraembryonic
mesoderm covering the yolk sac
• The somatic mesoderm and the overlying embryonic ectoderm form
the embryonic body wall or somatopleure
• Splanchnic mesoderm and underlying endoderm form the gut wall or
splanchnopleure
• during the second month the intraembryonic coelom is divided into
three cavities
• Pericardial cavity
• Pleural cavity
• Peritoneal cavity
BLOOD AND BLOOD VESSELS
• Blood vessels form in two ways: vasculogenesis, whereby vessels
arise from blood islands
• angiogenesis, which entails sprouting from existing vessels
• Formation begins in the extraembryonic mesoderm - yolk sac
connecting stalk and chorion
• Intraembryonic blood vessel formation
Further development of the chorionic villi
 Organogenetic period
• The fourth to eighth weeks
• All major external and internal structures are established
Phases of Embryonic Development
• Growth
• Morphogenesis
• Differentiation

Critical period for teratogens

Surface ectoderm
• epidermis and its appendages;
• adenohypophysis;
• sensory epithelium of the ear, nose, tongue;
• lens of the eye;
• enamel of the teeth.
Differentiation of mesoderm
mesoderm → Paraxial mesoderm → Somite
Intermediate mesoderm
Lateral mesoderm
somites ( 3 pairs/day, 42-44 pairs in total )
sclerotome → paraxial bones
dermatome → dermis
myotome → muscles
Intermediate mesoderm → primordium of the
urogenital system forming the kidneys and gonads,
etc.
Lateral mesoderm
1) Spaces appear and coalesce →
intraembryonic coelom → body cavities
 2)Somatic mesoderm → bones, muscles and
connective tissue of body wall, and mesothelium lining
inner surface of body wall.
3) Splanchnic mesoderm → muscles and connective
tissue of viscera, and mesothelium covering them.
Folding of the embryonic disc
rapid growth of CNS → head and tail folds
rapid growth of somites → lateral fold

cylindrical embryo
folds:
1) embryo bulges into enlarged amniotic cavity;
2) surface of embryo is wrapped by ectoderm;
3) endoderm forms a tube like gut invested into
embryo;
4) body stalk is reduced to form umbilical cord, by
which embryo is suspended in amniotic cavity.
 • Formation of primitive gut and differentiation of
endoderm
primitive gut
(  foregut, midgut, hindgut )
vitelline duct yolk sac
 primitive gut → primordium of digestive and
respiratory systems.

endoderm → epithelial of digestive & respiratory tract,

and bladder, urethra; parenchyma of liver, pancreas,
tonsil, thyroid, parathyroids, thymus; epithelium of
tympanic cavity and Eustachian tube.
INDUCTION
Cell movements during gastrulation
Mesoderm is patterned in a cranial to caudal gradient
Axial mesoderm: passes through the
node and migrates along the midline
–forms the notochord

Paraxial mesoderm: passes just

caudal to the node and migrates
slightly laterally –forms cartilage,
skeletal muscle, and dermis

Lateral plate mesoderm: passes more

caudal and migrates more laterally –
forms circulatory system and body
cavity linings.

Extraembryonic mesoderm: passes

most caudal and migrates most
laterally –forms extraembryonic
membranes and associated
connective tissue & blood vessels.
 Fate of the “axial” mesoderm
The notochord and pre-chordal plate develops from mesoderm arising from cells that passed
directly through the node and migrated cranially along the midline
The notochord and pre-chordal plate are important signaling centers that pattern the
overlying ectoderm and underlying endoderm.
 Major signaling centers at gastrulation:
the node and the anterior visceral endoderm (AVE)

• Primitive node positions primitive streak for gastrulation, induces neural differentiation
• AVE from primitive endoderm secretes factors that position primitive streak in posterior, induce head
formation
The node also sets up the neural plate
Head signaling centers

Prechordal plate~ early notochord

Left-Right asymmetry is established at
gastrulation
Leftward beating of cilia at node moves
secreted molecules sonic hedgehog (Shh)
& FGF-8 to the left side of embryo.

Causes left side genes Nodal and Pitx2 to

be expressed which then pattern
developing organs.

If cilia are defective, Shh and Fgf8 can

randomly end up on right side, resulting in
reversal of symmetry, aka situs inversus
(liver on the left, spleen on the right, etc.)

Situs can be complete (everything

reversed) or partial (only some organs
reversed).
Situs Inversus
What happens if there is “not enough” gastrulation?
Caudal agenesis (sirenomelia)
Premature regression of the primitive streak leads to widespread loss of trunk
and lower limb mesoderm.

VATeR association:
Vertebral defects
Anal atresia
Tracheo-esophageal fistula
Renal defects

VACTeRL association:
those above plus…
Cardiovascular defects
Limb (upper) defects
 What happens if there is “too much” gastrulation?
Sacrococcygeal teratoma
If the primitive streak fails to regress, multipotent primitive streak cells can develop into
multi-lineage tumors (containing ecto-, meso-, and endodermal tissues).
End of embryonic period
 Fetal membrane — overview
•Originate from blastocyst, don’t
participate in the formation of
embryo
•Including:
1) Chorion
2) Amnion
3) Yolk sac
4) Allantois
5)Umbilical cord
 Chorion
•Formed by
trophoblast +extraembryonic mesoderm
 Chorion
• Primary villi: cytotrophoblast+syncytiotrophoblast
• Secondary villi: extraembryonic mesoderm enter the
primary villi
• Tertiary villi: extraembryonic mesoderm =>CT+BV
Chorion frondosum-embryonic pole
Chorion laeve-abembryonic pole
 Function of Chorion
1) Exchange of metabolite:
portion of placenta (Chorion frondosum)
2) Hormone production:
human chorionic gonadotropin (HCG)
 Amnion
•Amniotic membrane: amniotic epi.+ extraembryonic mesoderm
•Amniotic fluid:
Produce:1)amniotic cells
2) infusion of fluid from maternal blood
3) urine output from the fetus
4) pulmonary secretions
Output: 1) absorbed by amniotic cells
2) fetus swallow

•1 liter – circulate
 Amnion - Fluid
• Functions
• Mechanically cushion
• Protect from fetus adhesion
• Movement
• Maintain Temp
• Abnormalities
1) too much (polyhydramnios)
>2000 ml
Abnormal digestive system or CNS
- esophageal atresia
- anencephaly
2) too little (oligohydramnios)
<500 ml
Abnormal urinary system
- poor development of kidney
- urethra atresia
 Yolk sac and Allantois
• Yolk sac
• Primitive Gut
• 3rd week, Germ Cells
• 3rd to 6th week,
Blood island
• Allantois
• Caudal extension of
hindgut
• Allantoic A pairs
• Allantoic V pairs

Umbilical vessels
2A+1V
Umbilical Cord
• Folding – a purse string
closure
• Amnion membrane covered
• Cord: mucous CT, 3
vessels,yolk sac ,allantois
• 50-60 cm, 2cm diameter
• Long – knots
• Short – abruption
Placenta - Overview
• Functions as:
• Lungs, GI tract, Liver, Kidneys, Endocrine
• Placenta proper:
Chorion frondosum+ Decidua basalis
 Anatomy of the Placenta

• Fetal – Chorion
• Chorion Frondosum
• Chorion Laeva
• Maternal – Decidua
• Decidua Basalis
• Decidua Capsularis
• Decidua Parietalis
Anatomy of the Placenta

• At birth 500 g
• 15-25 cm Diameter
• 3 cm thick
• Anchoring villi
• Decidual septa  15-20
Cotelydons
Placental-Fetal Circulation
• Fetus:
umbilical A carries O2/nutrient depleted blood to cap. of
chorion , exchange with maternal blood of the intervillous
spaceumbilical V
• Mother:
spiral A intervillous space uterine V
 Placental Barrier
--the structure between fetal and maternal blood
--components:
1)endothelium of chorion capillary
2) CT in the core of the villus
3) trophoblast epithelium
 Placental Function
1.Exchange of Metabolites: nutrients
antibody, waste
2.Defense barrier
3.hormone production
- human chorionic gonadotropin (HCG)
Begin: end of 2nd week
Highest: 2nd month
- Estrogen and progesterone
- Placental lactogen
Twins
Two types:
• One zygote (monozygotic)
• Two (or more) zygotes
(dizygotic)
• 2 (or more) oocytes
• Non Identical
Twins
- Monozygotic
• Zygote split
• 2-4 cell
• 2 amn, 2 chorion
• Blastocyst
• 2 amn, 1 chorion
• Bilaminar germ disc
• 1 amn, 1 chorion
• Incomplete splitting
• Conjoined twins
End of lecture