3 Week of Development

rd

Dr. Aftab Ahmad

Associate Professor Anatomy
Diagrammatic Over View of
1 Week of Development
st
1st Week
Diagrammatic Over View of
2 Week of Development
nd
8th Day of Development
8th Day of Development
Completion of Implantation
9th Day of Development
12th Day of Development
12th Day of Development
12th Day of Development

Extraembryonic coelom
Or Chorionic Cavity
Extraembryonic Mesoderm
13th Day of Development
13th Day of Development
14th Day of Development
Implantation
 3rd Week of Development
Developmental events of 3rd week are:
• Gastrulation
• Appearance of primitive streak
• Formation of notochord
• Neurulation
• Development of Somites
• Development of Intraembryonic coelom
• Early Development of Cardiovascular System
• Development of Chorionic Villi
Gastrulation
 Gastrulation

 Most characteristic event occurring

during the 3rd week of gestation is
gastrulation, process of formation
of three primary germ layers
(Endoderm, Mesoderm & Ectoderm)
 Gastrulation
 Begins with formation of primitive
streak on surface of epiblast (day
15-16) at caudal end of embryonic
disc

 Primitive streak can be seen

longitudinal midline as narrow
groove with slightly elevated
margins
 Primitive Streak

 Cephalic end of streak consists of small circular

elevated area called primitive node, surrounding the
small depression primitive pit
 Primitive Streak
After primitive streak formation,
embryo has:
 Longitudinal (Craniocaudal) axis
 Dorsal & ventral surfaces
 Right & left sides

Fate of Primitive streak:

 By the end of 4th week primitive
streak shows regression, rapidly
shrinks and soon disappears
 Mechanism of Gastrulation

• Invagination is inward movement of epiblast cells

towards primitive streak
• Upon arrival in the region of streak, these cells detach
from epiblast and slip beneath it
• Once invaginated, some cells displace hypoblast
creating embryonic endoderm
 Mechanism of Gastrulation
• Others come to lie between epiblast and newly formed
endoderm to form Mesoderm
• Cells remaining in the epiblast form Ectoderm
 Thus epiblast is the source of all three germ layers and
cells in these layers will give rise to all of the tissues and
organs of the body
Gastrulation
Gastrulation
Gastrulation
Gastrulation
 Gastrulation

Mesoderm intervene between

ectoderm and endoderm except these
regions:
• Oropharyngeal membrane
• Cloacal membrane
• Notochordal tube
 Forebrain: Diencephalon
 Gross Appearance :
• Diencephalon is
divided into four
major parts :
1. Thalamus
2. Subthalamus
3. Epithalamus
4. Hypothalamus
 Fate Map 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;
• Lateral edges of the node and from the cranial
end of the streak become paraxial mesoderm;
• Midstreak region become intermediate mesoderm;
• More caudal part of the streak form
lateral plate mesoderm;
• Caudal-most part of the streak
contribute to extraembryonic
mesoderm;
Fate Map During Gastrulation
Notochord Formation
 Notochord Formation
1. Formation of Notochordal Process.
2. Formation of Notochord from the
Notochordal Process.
• Those epiblastic cells, which enter the
primitive pit, give rise to a mesodermal
tube between the ectoderm and
endoderm; this tube is called notochordal
process.
 Notochord Formation(cont)
• Cranially, this process ends just short of
the prechordal plate.
• The notochordal process grows in length
as cells proliferating in the region of
primitive node are added on to its proximal
end.
• Cranially, this process ends just short of
the prechordal plate.
 Notochord Formation(cont)
 By the 18th day of development the floor of the
notochordal process fuses with the underlying
endoderm.
 The fused layers soon degenerate and
disappear, resulting in the loss of floor of the
notochordal process.
 The opening at the primitive pit now
temporarily connects the amniotic cavity and
umbilical vesicle (yolk sac); this communication
is called neurenteric canal.
 Notochord Formation(cont)
After the disappearance of the floor, the
roof of the notochordal process forms a
flattened midventral bar of mesoderm,
called notochordal plate, which lies in the
roof of the yolk sac intercalated between
the endodermal cells.
On days 22 to 24, the notochordal plate
detaches from the endoderm and
gradually rolls up to form a solid cord of
cells, which is called notochord.
 Formation of Notochord
 Notochord is a cellular cord that
defines the primitive axis of the
body
• Epiblastic cells which invaginate in
the cranial part of primitive pit are
known as prenotochordal cells

• These cells move forward cranially

in midline towards prechordal plate,
now called notochordal plate
 Prechordal Plate
• A small circular area of columnar endodermal cells where
the ectoderm and endoderm are fused

• The prechordal plate gives rise to the endoderm of the

oropharyngeal membrane, located at the future site of
the oral cavity
 Formation of Notochord

• As the hypoblast is replaced by endoderm cells, cells of

notcordal plate proliferate and detach from endoderm

• They form a solid cord of cells the definitive notochord

which lies in midline between ectoderm & endoderm
 Function & fate of Notochord
• Notochord is primary inducer for the
development of nervous system
(neural plate)

• Serve as basis for axial skeleton

• Defines primordial longitudinal axis of

embryo

• Contribute to intervertebral disc

between bodies of vertebra
 Function & fate of Notochord

• Notochord degenerates and disappear in the region of

developing vertebral bodies
Formation of Notochord
Formation of Notochord
 Neurenteric Canal
• At the point where the pit forms an indentation in
the epiblast the neurenteric canal temporarily
connects the amniotic and yolk sac cavities
 Cloacal Membrane
• The cloacal membrane is formed at the caudal end of
the embryonic disc

• The allantois appears on approximately day 16 as a

small diverticulum (outpouching) from the caudal wall
of the yolk sac that extends into the connecting stalk
 Allantois
• This diverticulum is Allantois/Allantoenteric
diverticulum appear around the 16th day of
development
 Allantois
• In humans, the allantoic sac remains very small, the
proximal part of the allantoic diverticulum persists
throughout as a stalk called the urachus, which extends
from the bladder to the umbilical region
 Allantois
• The urachus is represented in adults by the median
umbilical ligament

• The blood vessels of the allantoic stalk become the

Umbilical arteries
Neurenteric Canal
Intraembryonic Mesoderm
 Organization of intraembryonic
Mesoderm

• Mesoderm become organized into three segments in each

half of embryonic disc
Paraxial mesoderm
Intermediate mesoderm
Lateral mesoderm
Embryonic Mesoderm
 Growth of Embryonic disc
• Initially flat and almost round,
gradually becomes elongated with
broad cephalic and narrow caudal end

• This is due to continuous migration of

cells from primitive streak region in a
cephalic direction

• Invagination and migration continues

till the end of 4th week
 Further Development of
Trophoblast
• By the beginning of 3rd week, trophoblastic is
characterized by Primary chorionic villi (finger like
projections consisting of cytotrophoblastic core covered
by syncytiotrophoblat

• In early part of 3rd week, mesodermal cells penetrate the

core of primary villi, now referred as Secondary chorionic
villi
Further Development of
Trophoblast
 Further Development of
Trophoblast
• By the end of 3rd week, mesodermal cells begin to
differentiate into blood cells and vessels, now referred as
Tertiary Chorionic villi
• Vessels in tertiary villi are connected to the embryonic
heart through blood vessels

• Space surrounding chorionic villi is

called intervillous space
 Further Development of
Trophoblast
• Cytotrophoblastic cells in the villi penetrate progressively
in to overlying syncytiotrophoblast until they reach the
maternal endometrium, hence forming thin outer
cytotrophoblatic shell
• Chorionic cavity become larger
and embryo is attached to the
trophoblastic shell by a
connecting stalk later
develops into umbilical cord
Clinicals of Gastrulation
 Tumors Associated with
Gastrulation
• Sometimes, remnants of the primitive streak persist in
the sacrococcygeal region, these clusters of pluripotent
cells proliferate and form tumors, known as
sacrococcygeal teratomas,
• That terattomas commonly contain tissues derived from
all three germ layers
 Tumors Associated with
Gastrulation
• This is the most common tumor in newborns, occurring
with a frequency of one in 35,000
• Sacrococcygeal teratomas are usually diagnosed on
routine antenatal ultrasonography;
• Most tumors are benign, these teratomas are usually
surgically excised promptly, and the prognosis is good
 Teratogenesis Associated with
Gastrulation
• 3rd week of development, when gastrulation is initiated,
is a highly sensitive stage for teratogenic insult

(A teratogen is any agent that can produce a birth defect/

congenital anomaly or increase the incidence of a defect in
the population)
 Teratogenesis Associated with
Gastrulation
• For example, alcohol consumption in high doses at this
stage kill cells in the anterior midline of the germ disc,
producing a deficiency in craniofacial structures

• Gastrulation itself may be disrupted by genetic

abnormalities and toxic insults, this condition is
associated with maternal diabetes and other causes
 Remnants of Notochord
• 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
Neurulation
 Neurulation
 Neurulation is the process whereby
neural plate forms the neural tube

 Begins in the mid of 3rd week of

development, as notochord
develops, it induces overlying
ectoderm in the midline of
embryonic disc to thicken and
form neural plate
 Neurulation
 Ectoderm forming neural plate is referred as
neuroectoderm

 By the end of the third week the mid region of neural

plate becomes invaginated to form groove called
neural groove

 Whereas lateral margins of

plate become elevated to form
neural folds
 Neural tube
 The neural folds approach
each other in the midline
where they fuse and
neural tube is formed in
early 4th week

 Fusion begins in cervical region (5th somite) and

proceeds cranially and caudally

 Neural tube soon separates from surface ectoderm

 Neural tube
 The neural tube communicates with amniotic cavity at
its cranial and caudal ends through anterior/cranial
neuropore and posterior/caudal neuropore
respectively
 Neural tube
 Anterior neuropore closes on 25th day and posterior
neuropore closes on 28th day
 Neural tube
 Closure of neuropore completes the
process of neurulation by the end of
4th week

 Neural tube is the primordium of

CNS, dilated cranial part of tube is
primordium of brain and narrow,
longer caudal portion develops in to
spinal cord
 Neural Crest Cells
 When neural folds elevate and
begin to fuse, the neuroectoderm at
lateral margins of each fold give rise
to special population of cells called
Neural Crest Cells

• As neural tubes detaches from

surface ectoderm, the neural crest
cells dissociate from their neighbors
and migrate in dorsal as well as ventral
direction
 Neural Crest Cells

1) 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.

2) 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 When neural
Neural Crest Cells
 Neural Crest Derivatives
• Connective tissue & bones of face
and skull
• Cranial nerve ganglia
• C cells of thyroid gland
• Conotruncaal septum in heart
• Odontoblast
• Dermis in face & neck
• Spinal (dorsal root) ganglia
• Sympathetic chain and preaortic
ganglia
 Neural Crest Derivatives
• Parasympathetic ganglia of GIT
• Adrenal medulla
• Schwann cells
• Glial cells
• Meninges
• Melanocytes
• Smooth muscle cells to blood
vessels of face and forebrain
Neural Tube Defects
 Neural Tube Defects

• Neural plate is the primordium of the CNS and gives

rise to the neural folds and the beginning of the neural
tube, disturbance of neurulation may result in severe
birth defects of the brain and spinal cord

• Neural tube defects are among the most common

congenital anomalies
 Neural Tube Defects
 Results when neural tube closure
fails to occur
• If neural tube fails to close in cranial
region, most of the brain fails to
form, the defect is called
Anencephaly
• If closure fails anywhere from
cervical region caudally, then the
defect is Spina bifida
• Most common site for spina bifida is
lumbosacral region
 Neural Tube Defects
 Anencephaly is a lethal defect and
most of cases are diagnosed
prenatally and the pregnancies
terminated

 Rate of occurrence have been

reduced significantly following folic
acid administration, beginning 3
months prior to conception and
continuing through out pregnancy
Endovaginal sonogram (sagittal and axial) of an early chorionic
(gestational) sac
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