DAY 12

The blastocyst is completely embedded in the endometrial stroma, and the surface epithelium
almost entirely covers the original defect in the uterine wall.
Blastocyst produce a slight protrusion into the lumen of uterus
Extraembryonic mesoderm eventually fills all the space between trophoblast externally and the
amnio and exocoelomic membrane internally. Soon, large cavities appears: called
extraembryonic coelom/ chorionic cavity.
Extraembryonic somatopleuric mesoderm: line cytotrophoblast and amnion.
Extraembryonic splanchnopleuric mesoderm: covering yolk sac.

DAY 13

Extraembryonic somatic mesoderm + trophoblast = chorion

Extraembryonic mesoderm lining the inside of the trophoblast = known as chorionic plate
A small secondary yolk sac has formed inside the primitive yolk sac as it is pinched off thus
decreasing the primitive yolk sac.
DAY 14

The definite yolk sac is much smaller than the primitive yolk sac.
Exocoelomic cyst are often found in the extraembryonic coelom/chorionic cavity.

Detail ( day 14 )

In its cephalic region the hypoblastic disc shows a slight thickening known as buccopharyngeal
membrane. This area of columnar cells that are firmly attached to the overlying epiblastic disc.
PREGNANCY TEST
Synciotrophoblast = secrete human chorionic gonadotropin (HCG).
End of 2nd week quantities of this hormone are sufficient to be detected by pregnancy testing.
3rd WEEK UNTIL 8TH WEEK ( EMBRYONIC PERIOD)
Gastrulation:process that establish all 3 germ layers( ectoderm,endoderm,mesoderm)

Begins with formation of primitive streak on the surface of epiblast. The streak is vaguely
defined.

DAY 15-18

The primitive streak is clearly visible as a narrow groove with slightly bulging regions on either
side.
The cephalic end of the streak, the primitive node , consist of slightly elevated area surrounding
the small primitive pit.
Figure A- cells of the epiblast migrate toward the primitive streak (black solid line). Broken line
shows the subsequent migration of cells between the hypoblast and epiblast.
Figure B- Cross section at the cranial region of the streak:
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.
Additional info: cell migration and specification are controlled by fibroblast growth factor 8 ( FGF8),
which is synthesized by streak cells themselves. It controls cell movement by downregulating E-cadherins
( protein that normally binds epiblast together) . FGF8 also control specification into the mesoderm by
regulating Brachyury(T) expression.

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.
Epiblast source of all the germ layers (gastrulation).

FORMATION OF NOTOCHORD

Prenotochordal cells migrate cranially

from the primitive knot and form a
midline cord known as notochordal
process.
This cord grows between ectoderm
and endoderm until it reaches the
prechordal plate, which indicates the
future site of the mouth
The notochordal process can extend no
further because the prechordal plate is
firmly attached to the overlying
ectoderm,forming oropharyngeal
membrane.
The cloacal membrane is formed at
the caudal end of the embryonic disc.
This membrane, which is similar in
structure to the oroparyngeal
membrane, consists of tightly adherent
ectoderm and endoderm cells with no
intervening mesoderm.

The notochord defines the primitive axis of the

embryo:

In lower chordate it forms the skeleton

of a grown animal.
In human embryo it forms a midline axis
and the basis of the axial skeleton (
vertebral column ,ribs , sternum and the
skull)

By the end of the 4th week the notochord is

almost completely formed and extends from
the oropharyngeal membrane cranially to
the primitive node caudally

The notochord degenerates and

disappears where it is surrounded by
the vertebral bodies, but persists as
the nucleus pulposus of each
invertebral disc. The notochord also
induces the overlying ectoderm to
form the neural plate , the
primodium of the CNS.

DEVELOPMENT OF THE ECTODERM.

NEURULATION: process whereby the neural plate forms the neural tube.
A (day 17) _ embryonic ectoderm over it
thickens to form the neural plate giving rise to
the CNS.

B (day 18)- the neural plate invaginates along

its central axis to form a neural groove with
neural folds on both sides.

By the end of the 3rd week , the lateral edges of the neural plate become elevated to form
neural folds , and the depressed mid region forms the neural groove.

Gradually , the neural folds approach each other in the midline , where they fuse.
Fusion begins in the cervical region (5th somite) and proceeds cranially and caudally.
As a result, the neural tube is formed.
Until fusion is complete, the cephalic and caudal ends of the neural tube communicate with the
amniotic cavity by way of the anterior(cranial) and posterior(caudal) neuropores, repectively.
Closure of the cranial neuropore occurs at approximately at day 25( 18-20 somite stage),
whereas the posterior neuropore closes at day 28 (25 somite stage).
CNS is represented by a closed tubular structure with a narrow caudal portion- spinal cord

And much broader cephalic portion characterized by a number of dilations- the brain vesicles.
The ectodermal neural cretson
each side approach each other
and fuse as the tube below the
surface.
Some of these cells(neural crest
cell) will pinch off and migrate to
form ganglia throughout the
trunk and variety of other tissues
in the head and neck. Neurulation
advances both cranially and
caudally.

Additional info about neural crest cells : as the neural folds elevate and fuse , cells at the crest of the neuroectoderm
begin to dissociate from their neighbors and will undergo an epithelial-to-mesenchymal transition as it leaves the
neuroectoderm by active migration and displacement to enter the underlying mesoderm. (mesoderm refers to cells
derives from the epiblast and extraembryonic tissues. Mesenchyme refers to loosely organized embryonic connective
tissue regardless of origin. Crest cell from the trunk region leave the neuroectoderm after closure of the neural tube
migrate along 1 of the 2 pathway :
a)

a dorsal pathway through the dermis, where they will enter the ectoderm through holes in the basal lamina to
form melanocytes in the skin and hair follicles.
b) A ventral pathway through the anterior half of each somite to become sensory ganglia,sympathetic and enteric
neurons , Schwann cells, and cells of the adrenal medulla.
c) Also form and migrate from cranial neural folds, leaving the neural tube before closure in these region. These
cells contribute to the craniofacial skeleton, as well as neuron for cranial ganglia, glial cells, melanocytes and
other types.

Initially continuos across the midline, the

neural crest soon separates into right and
left parts. The two parts of the neural crest
migrate to the dorsolateral aspect of the
neural tube, where they give rise to the
sensory ganglia.

DERIVATIVE OF THE NEURAL CREST

Sensory neuron in the PNS.
Postsynaptic autonomic neurons of the PNS
Schwann cells
Head mesenchyme
Melanocytes in the skin
Arachnoid and pia mater of meninges (dura mater
from mesoderm)

DERIVATIVE OF THE NEURAL TUBE

Supporting cells of the CNS
Presynaptic autonomic neurons of the PNS
Neurons of the CNS
Somatomotor neurons of the PNS
-

DEVELOPMENT OF THE MESODERM

Figure A: Initially, cells of the mesodermal germ layer form a thin sheet of loosely woven tissue on each
side of the midline. On the 17th day, cells close to the midline proliferate and form a thickened plate of
tissue known as paraxial mesoderm(future somites). Figure B: More laterally, the mesoderm layer
remains thin and is known as the lateral plate. Figure C : Tissue is then divided into 2 layers :

A layer continuous with mesoderm covering the amnion = somatic/parietal mesoderm layer
A layer continuous with mesoderm covering the yolk sac= splanchnic/visceral mesoderm layer

Figure D : These layers line a newly formed cavity= intraembryonic cavity.

Intermediate connect paraxial and lateral plate mesoderm

day 17

day 19

DAY 20

DAY 21

FOLDING OF THE EMBRYO

DAY 21-22 : Cephalocaudally folding, from essentially flat

pan-cake disc to a sylindrical configuration. Tremendous
growth of the future brain region results in formation of
the head fold and tail fold along the sagittal plane of the
embryo.

Day 23-24 : during the head folding a part of the yolk sac
is incorporated into the embryo as a foregut which ends
bindly at the oropharyngeal membrane . this membrane
separates the foregut from the stomodeum (primitive
mouth cavity). At the end of the 1st month this
membrane ruptures thus establishing an open
connection between the amniotic cavity nd the primitive
gut.

Day 25- more and more of the yolk sac is

incorporated and the foregut with the
hindgut lengthen at the expence of the
midgut.

At the end of 4th week, cells of the somatic mesoderm lining the intraembryonic coelom,become
mesothelial and form parietal layer of the serous membrane ( lining the outside of the future peritoneal,
pleural and pericardial cavities).
Cells of the splanchnic mesodermal layer form the visceral layer of he serous membranes covering the
abdominal organs, lungs and heart. Visceral and parietal layers are continuous with each other as the
dorsal mesentery is a result of thinning of septum transversum.
MESODERMAL LAYER- Originates from the primitive streak and node and forms through gastrulation
and invagination of the epiblast cells.
Paraxial mesoderm begins to be organized into segments known as somitomeres by the end of 3rd
week. First appear in the cephalic region of the embryo and their formation proceeds cephalocaudally.
Each somitomere consists of mesodermal cells arranged in concentric whorls around the center of the
unit.
Head region: somitomeres form in association with segmentation of the neural plate into neuromeres.
From occipital region caudally : somitomeres further organize into somite.
Intermediate mesoderm temporarily connects paraxial mesoderm with the lateral plates. It will
differentiates into urogenital structures.
In cervical and upper thoracic regions: forms segmental cell clusters( future nephrotomes) whereas
more caudally , it forms an unsegmented mass of tissue , the nephrogenic cord.
Lateral plate mesoderm splits into parietal(somatic): line the intraembryonic cavities and
visceral(splanchnic) : surround the organs.
1) Parietal layer + overlying ectoderm : forms the lateral body wall folds and close the ventral body
wall. (picture above) .
Parietal layer of lateral plate mesoderm then forms the bones and connective tissue of the limbs and
sternum. Sclerotome+precursor cells= migrate into the parietal layer : form the costal cartilages, limb
muscles and most of the body wall muscles. It also surrounding the intraembryonic cavity form thin
membranes- mesothelial membranes/serous membranes ( line the peritoneal ,pleural and pericardial
cavities and secrete serous fluid)

2) Visceral layer+ embryonic endoderm = forms the wall of the gut tube
= also form a thin serous membrane around each organ
Blood and blood vessels ( also arise from mesoderm) form in 2 ways

Vasculogenesis vessels arise from blood islands.

Angiogenesis which entails sprouting from existing cells.

FORMATION OF SOMITES (PARAXIAL MESODERM) begin at 3rd week.

When somites first from paraxial mesoderm, they exist as a ball of mesoderm cells ( fibroblast
like).
Then, it undergo a process of epithelization and arranged themselves in a donut shaped around
a small lumen.
Differentiates into :
a) Myotome- limb and body wall muscle
b) Sclerotome- vertebral column, ribs and base of skull
c) Dermatome - Dermis of the skin.
A 14-somite embryo:
Formation of pericardial bulge and
pharyngeal arches
B 25-somite embryo
Closure of neuropores. The 1st three
pharyngeal arches and lens and otic
placode are visible

Eg:

Summary : FORMATION OF SOMITES (3rd -5th week)

Segmented block of paraxial mesoderm.

3 pairs develop per day in craniocaudal sequence.
Total: 42-44 pairs at the end of 5th week
occipital
4
Cervical
8
Thoracic
12
Lumbar
5
Sacral
5
Coccyx
8-10
st
The 1 occipital and the last 5-7 coccygeal somites later disappear, while the remaining somites
form the axial skeleton.
Because somites appear with a specified periodicity, the age of an embryo can be accurately
determined during this early time period by counting somites.
DERIVATIVE OF THE ENDODERMAL GERM LAYER (GIT)
As a result of cephalocaudal folding, a continuous larger portion of the endodermal germ layer
is incorporated into the body of the embryo to form the gut tube. The tube is divided into 3
regions : foregut , midgut and hindgut.
Midgut : communicates with the yolk sac by way of a broad stalk, the vitalline duct ( initially
wide, further growth and it become narrow and longer)
Foregut: temporarily bounded by an ectodermal-endodermal membrane called oropharyngeal
membrane (separates the stomadeum , the primitive oral cavity(ectoderm) , from the pharynx
and a part of foregut(endoderm). In the 4th week , this membrane ruptures , establishing an
open connection between the oral cavity and primitive gut.
Hindgut: terminates temporarily at an ectodermal-endodermal membrane , the cloacal
membrane ( separates the upper part of the anal canal(endoderm) from the lower part (called
proctoderm). The membranes break down in the 7th week to create the opening for the anus.

SUMMARY : DERIVATION OF 3 GERM LAYER

ECTODERM
CNS and skin.
Epithelial of the skin and glands

MESODERM
Supporting tissue ( CT, cartilage
and bones
Striated and smooth muscle
Blood and lymph cells
Wall of the heart, blood and
lymph vessel
Kidney, gonads and
corresponding ducts
Cortex of suprarenal gland and
spleen

ENDODERM
Epithelial lining of GIT and respi
tract, urinary bladder , tympanic
cavity and auditory tube
Parenchyma of the tonsil,
thyroid and parathyroid glands,
thymus, liver and pancreas.
Reticular stroma of the tonsils
and thymus.

STAGE 14 WEEK 5 (DAY31-35)

-embryonic periodtapering upper limb buds

STAGE 16 , WEEK 6 (DAY 38-42)

-embryonic periodThigh, leg and foot canbe distinguishes in the
lower limb.

STAGE 18 , WEEK 7 (DAY 44-48)

-embryonic period* ossification of he skeleton begins.
* cervical and lumbar flexures
* distinct notching in the hand plate
* the 1st appearance of the elbow
* spontaneous movement

STAGE 19 , WEEK 8 (~DAY 48-51)

Embryonic period
Straightening of the trunk
The limbs extend nearly directly forward
Toe rays are prominent but interdigital have
not yet appeared in the foot.

STAGE 20 , WEEK 8 (DAY 51-53)

Embryonic period
Brain activity brain is connected to tiny muscles
and nerves and enables the embryo to make
spontaneous movements.
Anal membrane is perforated. Testes or ovaries are
distinguishable.

STAGE 23 , WEEK 8 (DAY 56-60)

Last stage of embryonic period
All essential external and internal structures are
present

FETAL PERIOD ( WEEK 9 UNTIL BIRTH)

Time of extensive growth in size, differentiation of organ system established in the embryonic period.
Brain continues to grow and develop, respi system differentiates, the urogenital further differentiates
the male/female , endicrine and GIT begins to function.
EMBRYONIC PERIODFETAL PERIOD ( WEEK 8 ++)

The risk of miscarriage decrease sharply at the beginning of the fetal stage.
All major structures , including hands, feet, head , brain and other organs are present
continue to grow and become more functional.
Fetal stage (30mm) heart is beating

WEEK 8+ 3 DAYS (25.4mm)

The fingerprint formation can be seen from the
beginning of the fetal stage

24.5mm

25mm

26mm

(WEEK 8+ DAY 5)
Upper and lower limbs are well formed. Fingers get longer and toes no longer webbed and all
digits are separate and distinct. Tail has disappeared. Appearance is human. Taste buds begin
to form on the surface of the tongue. The primary teeth are at cap stage. Bones of the palate
begin to fuse. External genitals still difficult to recognize.

FETAL PERIOD
WEEK 9
Fetus is able to bend fingers around an object. Layer of
rather flattened cells, the precursor of the surface layer of
the skin, replaces the thin ectoderm of the embryo. Fetus
in the amniotic sac exposed by removal from the chorionic
sac. The different appearance of the genitals in males and
females become pronounced.
Genitalia begin to show female characteristics and male
characteristics. Neither male nor female are fully formed.

WEEK 9