Third week

The third week

• Rapid development of the embryo

◦ Appearance of primitive streak
◦ Differentiation of three germ layers
◦ Development of notochord.
Gastrulation

◦ the formative process by which the three germ layers and axial
orientation are established in the embryos
◦ Bilaminar embryonic disc is converted into a trilaminar embryonic
disc
◦ beginning of morphogenesis (development of body form)
◦ begins with formation of the primitive streak on the surface of the
embryonic disc
Primitive Streak

▶Primitive streak : due to Proliferation and migration of

cells of the epiblast to the median plane of the
embryonic disc
▶Primitive node : Proliferation of cells at the cranial end
of primitive streak
▶Primitive groove : Narrow groove in the primitive streak
▶Primitive pit : Small depression in the primitive node
 Embryonic
ectoderm

Prechordal plate
Primitive streak
Notochordal
process

Primitive node

Primitive streak

Primitive groove
Formation of mesenchyme

▶after the primitive streak appears, cells leave its deep

surface and form mesenchyme,
▶ tissue consisting of loosely arranged cells suspended in a
gelatinous matrix

▶Mesenchyme forms the connective tissues of the body and

glands.

▶Formation of mesoblasts
epiblast, give rise to all three germ layers in the embryo, the
primordia of all its tissues and organs

▶Mesoblasts form the intraembryonic, or embryonic mesoderm

▶Cells from the epiblast displace the hypoblast, forming the

intraembryonic, or embryonic endoderm in the roof of the
yolk sac

▶The cells remaining in the epiblast form the intraembryonic, or

embryonic ectoderm
Fate of Primitive Streak

▶The primitive streak actively forms mesoderm until the

early part of the fourth week;
▶production of mesoderm slows down

▶diminishes in relative size and becomes an insignificant

structure in the sacrococcygeal region of the embryo

▶Disappears by the end of fourth week

Clinical importance

Sacrococcygeal teratoma :
▶tumor arises from remanent of
primitive streak.
▶ contains various types of tissues
( bone ,nerve , hair )
GERM LAYER DERIVATIVES
• Ectoderm
▶Central nervous system
▶Peripheral nervous system;
▶Sensory epithelia of the eye, ear, and nose;
▶Epidermis and its appendages (hair and nails);
▶Mammary glands;
▶Pituitary gland;
▶Subcutaneous glands; and
▶Enamel of teeth
Mesoderm
• Connective tissue
• Cartilage
• Bone
• Striated and smooth muscles
• Heart, blood, and lymphatic vessels
• Kidneys
• Ovaries, testes, genital ducts.
• Serous membranes lining the body cavities
• Spleen
• Cortex of suprarenal glands.(not the medulla which is in endoderm)
Endoderm
▶Epithelial lining of the gastrointestinal and respiratory tracts.

▶Parenchyma of the tonsils, thyroid and parathyroid glands, thymus,

liver, and pancreas.

▶Epithelial lining of the urinary bladder and most of the urethra.

▶Epithelial lining of the tympanic cavity, tympanic antrum, and

pharyngotympanic (auditory) tube.
ALLANTOIS
• appears on approximately day 16
• small diverticulum from the caudal
wall of the umbilical vesicle.
• The proximal part persists as the
urachus, which extends from the
bladder to the umbilical region
• the median umbilical ligament.
• The blood vessels of the allantoic
stalk become umbilical arteries.
▶By the middle of the third week, intraembryonic mesoderm
separates the ectoderm and endoderm everywhere except:

◦ At the oropharyngeal membrane cranially

◦ In the median plane cranial to the primitive node, where the notochordal
process is located

◦ At the cloacal membrane caudally

Notochord

▶Some mesenchymal cells migrate cranially from the primitive node

and pit, forming a median cellular cord, the notochordal process

▶This process soon acquires a lumen, the notochordal canal

▶The notochordal process is now a cellular tube that extends cranially

from the primitive node to the prechordal plate
Embryonic Notochordal
ectoderm process Primitive pit Connecting stalk

Cardiogenic Embryonic Allantois

(heart- endoderm
forming) area
 Cloacal membrane

Notochordal canal Embryonic endoderm

▶The floor of the notochordal process fuses with the underlying
embryonic endoderm.
▶The remains of the notochordal process form a flattened, grooved
notochordal plate

▶Beginning at the cranial end of the embryo, the notochordal cells

proliferate and the notochordal plate enfolds to form the notochord.
 Neural plate Neurenteric canal

Primitive streak

Cloacal
membrane

Oropharyngeal
Embryonic endoderm
membrane
Notochord
Neural groove ◦ Defines the primordial axis of the
embryo and gives it some rigidity
Notochordal
plate infolding
◦ Serves as the basis for development
of the axial skeleton (bones of head
and vertebral column)

◦ Indicates the future site of the

vertebral bodies
Tumor of notochord
▶The notochord persists as the nucleus pulposus of each
intervertebral disc. (this is the reminant of notochord)

Chordoma :
▶Tumor that arises from the remnants of notochord found either
intracranially or sacral region
Neurulation
• It begins in the third week.
• The notochord induces the overlying ectoderm to form neural plate
• the neural plate invaginates to form a longitudinal median neural
groove, which has neural folds on each side.
• first signs of brain development.
• the neural folds fuse, converting the neural plate into a neural tube,
the primordium of the CNS .
• Neural crest cells undergo an epithelial to mesenchymal transition
and migrate away .
• The surface ectoderm differentiates into the epidermis.
• Neurulation is completed during the fourth week
Neural crest cells
▶Derived from neuroectoderm.
▶Cells of the spinal, cranial (cranial nerves V, VII, IX, and X)
▶Autonomic ganglia
▶ Cells of the peripheral nervous system
▶Pigment cells of the dermis
▶Muscle, connective tissues, and bone of pharyngeal arch origin
▶Suprarenal medulla;
▶Meninges of the brain and spinal cord.
▶The cranial neural tube develops into the brain.

▶Fusion of the neural folds in the cranial region and closure of the rostral
neuropore form three primary brain vesicles from which the brain
develops .

The three primary brain vesicles form the:

▶ forebrain (prosencephalon)
▶ midbrain (mesencephalon)
▶ hindbrain (rhombencephalon)
Spinal Cord
▶Spinal cord has 3 layers ▶The mantle layer later forms
Neuroepithelial, Mantle, and the gray matter of the spinal
Marginal Layers. cord

▶Once the neural tube closes, ▶The outermost layer of the

neuroepithelial cells begin to give spinal cord, the Marginal layer,
rise to neuroblasts. contains myelinated nerve
fibers white matter
▶They form the Mantle layer, a zone
around the neuroepithelial layer.
Basal, Alar Plates
▶each side of the neural tube shows
a ventral and a dorsal thickening.
▶ The ventral thickenings - the Basal
plates - ventral motor horn cells.
▶The dorsal thickenings - the Alar
plates - the sensory areas.
▶A longitudinal groove, the sulcus
limitans, marks the boundary
between the two
Peripheral Nervous System
▶The PNS consists of cranial, spinal, and visceral nerves and cranial,
spinal, and autonomic ganglia.
▶Develops from various sources, mostly from the neural crest.
▶All sensory cells (somatic and visceral) of the PNS are derived from
neural crest cells.
▶12 pairs of cranial nerves form during the fifth and sixth weeks
Clinical Corner
•Spina Bifida Cystica (occulta)
•protrusion of the spinal cord and/or meninges through defects in the
vertebral arches, cyst-like sac that is associated with these anomalies.

•Spina bifida with meningocele

•When the sac contains meninges and CSF.
• The spinal cord and spinal roots are in their normal position, but there may
be spinal cord abnormalities.

•Spina bifida with meningomyelocele

•If the spinal cord and/or nerve roots are included in the sac.
•Associated with high Alpha-feto protein(AFP)
Caudal Dysgenesis (Sirenomelia; Mermaid Syndrome)

• If gastrulation stops too soon,

• These babies die due to (renal
agenesis).

• These defects are very rare.

• observed in infants from

diabetic mothers (insulin
dependent; type I)
Anencephaly

• the cranial end of the neural

tube fails to close.
• Brain tissue forms abnormally
and then degenerates due to
exposure to amniotic fluid and
lack of blood supply.
• The defect is lethal.
• Most of these cases are
diagnosed prenatally, and the
pregnancy is usually terminated.
Holoprosencephaly Lissencephaly

• Failure of the embryonic forebrain

(prosencephalon) to separate into 2
cerebral hemispheres; • Failure of neuronal migration
• mutations in sonic hedgehog signaling resulting in a “smooth brain”
pathway. (Cause) that lacks sulci and gyri.
• Associated symptoms: cleft lip/palate
and cyclopia.
• May be associated with
• high risk for pituitary dysfunction
(e.g., diabetes insipidus). microcephaly, ventriculomegaly.

• Can be seen with Patau syndrome

(trisomy 13).
Posterior fossa malformations Chiari 1 and 2
Chiari I malformation

• Ectopia of cerebellar tonsils

inferior to foramen magnum.
• Congenital, usually
asymptomatic in childhood,
manifests in adulthood with
headaches and cerebellar
symptoms.
• Associated with spinal
cavitation's (e.g., syringomyelia)
Chiari II malformation

• Herniation of cerebellar vermis

and tonsils (2 structures)
through foramen magnum with
aqueduct stenosis, They will
narrow the aqueduct
• noncommunicating
hydrocephalus.
• associated with lumbosacral
myelomeningocele. Bulging of
spinal cord, meninges and fluid.
• More severe than Chiari I,
usually presents early in life.
Dandy-Walker malformation

• Agenesis (fail to develop) of

cerebellar vermis
• cystic enlargement of 4th
ventricle
• fills the posterior fossa.
• Associated with
noncommunicating
hydrocephalus, spina bifida.
 Syringomyelia
• A Cystic cavity (syrinx) within central
canal of spinal cord
• Fibers of(spinothalamic tract) damaged
first.
• Results in “capelike,” bilateral,
symmetrical loss of pain and temperature
sensation in upper extremities.
• Associated with Chiari I malformation&
scoliosis.
• acquired causes include trauma and
tumors.
• Most common location cervical >
thoracic >> lumbar