Third week

Formation of germ layers and early tissue & organ

differentiation- the third week

• Rapid development of the embryo from the embryonic

disc during the third week is characterized by:

◦ 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 : 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

▶ Shortly after the primitive streak appears, cells leave its

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

▶ Mesenchyme forms the supporting tissues of the embryo,

such as most of the connective tissues of the body and the
connective tissue framework of glands

▶ Formation of mesoblasts
epiblast, through the process of gastrulation, 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; thereafter production of mesoderm
slows down

▶ The primitive streak 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 :
▶Is a tumor that arises from
remanent of primitive streak ,
often 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.
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
Notochordal
embryo and gives it some rigidity
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
▶ The proximal part of the notochordal canal persists temporarily as
the neurenteric canal which forms a transitory communication
between the amniotic and yolk sac cavities

▶ When development of the notochord is complete, the neurenteric

canal obliterates

▶ The notochord becomes detached from the endoderm of the yolk

sac, which again becomes a continuous layer
▶ The notochord degenerates and disappears as the bodies of the
vertebrae form, but it persists as the nucleus pulposus of each
intervertebral disc.

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 along its central axis to form a
longitudinal median neural groove, which has neural folds on each
side.
• are the first signs of brain development.
• By the end of the third week, the neural folds have begun to move
together and 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 .
• Subsequently, 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)
▶ The neural canal, the lumen of the neural tube, becomes the ventricles
of the brain and the central canal of the spinal cord.

▶ The walls of the neural tube thicken by proliferation of its

neuroepithelial cells.

▶ These cells give rise to all nerve and microglial cells in the CNS.

▶ The microglia differentiate from mesenchymal cells that enter the CNS
with the blood vessels.
Spinal Cord
▶ Neuroepithelial, Mantle, and Marginal
Layers.
▶ Once the neural tube closes,
neuroepithelial cells begin to give rise
to neuroblasts.
▶ They form the Mantle layer, a zone
around the neuroepithelial layer.
▶ The mantle layer later forms the gray
matter of the spinal cord
▶ The outermost layer of the spinal
cord, the Marginal layer, contains
nerve fibers emerging from
neuroblasts in the mantle layer.
▶ As a result of myelination of
nerve fibers, this layer takes on a
white appearance and therefore
is called the white matter of the
spinal cord
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.
▶ Twelve pairs of cranial nerves form during the fifth and sixth weeks
Clinical Corner
•Spina Bifida Cystica
•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.
•Ass with high Alpha-feto protein(AFP)
Caudal Dysgenesis (Sirenomelia; Mermaid Syndrome)

• If gastrulation stops too soon,

• In fact, the lower limbs are
fused into one because of the
lack of cells.
• These babies die due to (renal
agenesis).
• These defects are very rare
• observed in infants from
diabetic mothers (insulin
dependent; type I)
Anencephaly

• The defect arises when 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. that lacks sulci and gyri.
• Associated with 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 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
• noncommunicating hydrocephalus.
• associated with lumbosacral
myelomeningocele.
• More severe than Chiari I, usually
presents early in life.
Posterior fossa malformations
Dandy-Walker malformation
• Agenesis 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 a “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