rd

3 week development
 Learning objectives
• Describe the Formation & fate of primitive streak.
• Draw a concept map highlighting the sequence of events
responsible for transformation of bilaminar germ disc into
trilaminar germ disc.
• Describe the embryology behind sacrococcygeal teratoma and
justify its clinical picture.
• Describe the molecular factors responsible for gastrulation.

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 Formation of Trilaminar Germ Disc – 3rd week of
Development
• Gastrulation- most characteristic feature during 3rd
week
• 3 germ layers are established- ectoderm, endoderm
and mesoderm
• Start with formation of PRIMITIVE STREAK

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 PRIMITIVE STREAK
• Midline groove at
epiblast(15-16
days)
• Cephalic
end-primitive node
• Migration of
epiblast
(invagination) at
the region of
primitive streak;
migrating epiblast
cells form the
intraembryonic
mesoderm, replace
hypoblast(endoder
m)

4
 Gastrulation
• Gastrulation occurs during the third week of gestation.
• Gastrulation initiates with the formation of the primitive streak on
the epiblast.
• Cells migrate towards the primitive streak and undergo
invagination.
• Upon arrival in the region of the streak, they become flask-shaped,
detach from the epiblast, and slip beneath it
• Fibroblast growth factor 8 (FGF8) controls cell movement and
specification into mesoderm.
• Some cells displace the hypoblast to form embryonic endoderm,
while others form mesoderm between the epiblast and endoderm.
• Remaining epiblast cells form ectoderm.

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• As more and more cells move between the epiblast and
hypoblast layers, Cells spread laterally and cranially,
establishing contact with extraembryonic mesoderm.
• In the cephalic direction, cells pass on each side of the
prechordal plate.
• The prechordal plate forms between the notochord tip
and oropharyngeal membrane, essential for forebrain
induction.
• The oropharyngeal membrane represents the future
opening of the oral cavity.

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 Invagination mechanism
• Cell migration and specification is controlled
by FGF-8 secreted by streak
• It down regulates E- cadherin a protein that
binds epiblast cells togethers
• Hence facilitating migration of epiblast cells
• FGF -8 then causes cell specification into
mesoderm by brachyury-T expression

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 SACROCOCCYGEAL TERATOMA

• Persistence of
primitive
streak that
proliferates
and forms
new growth at
the
sacrococcygea
l area
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 SACROCOCCYGEAL TERATOMA

• These tumors may also arise from primordial

germ cells (PGCs) that fail to migrate to the
gonadal ridge

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 Learning objectives
• Describe the Invagination and movement of prenotochordal
cells
• Describe the Notochordal plate formation
• Describe the Neuroenteric canal formation
• Describe the fate of the notochord
• Describe the Establishment of body axis
• Draw and label the fate map establishment
• Describe the Fate map establishment
• Describe the molecular basis for notochord formation

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 Learning objectives
• Describe the role of notochord as an inducer
• Describe the embryological basis for situs
inversus, Sirenomelia, holoprosencephaly
• Describe the development of trophoblast and
chorionic villi during 3rd week of development

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 Notochord formation
• Prenotochordal cells invaginate in the primitive
node and move cranially in the midline until they
reach the prechordal plate.
• These cells become intercalated in the hypoblast,
forming the notochordal plate, consisting of two
cell layers briefly.
• As endoderm cells replace the hypoblast, cells of
the notochordal plate proliferate and detach,
forming the definitive notochord.
• The notochord extends cranially to the prechordal
plate and caudally to the primitive pit.
• Elongation of the notochord starts with the cranial
end first, with caudal regions added as the
primitive streak assumes a more caudal position.
• The notochord underlies the neural tube and
serves as a signaling center for inducing the axial
skeleton.
• The neurenteric canal temporarily connects the
amniotic and yolk sac cavities at the point where
the primitive pit forms an indentation in the
epiblast.
 NOTOCHORD

• Start from primitive

pit cephalad to
prechordal plate
• Start as notochordal
process which
transform to solid
cord of cells
• Serves as basis for
axial skeleton
• Form midline axis
• Inducer substance
for
neuroembryology

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• The notochordal process elongates by
invagination of cells from the primitive pit.
• The primitive pit extends into the notochordal
process, forming a notochordal canal.
• The notochordal process is now a cellular tube
that extends cranially from the primitive node
to the prechordal plate.

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• The floor of the notochordal process fuses
with the underlying embryonic endoderm.
• The fused layers gradually undergo
degeneration, resulting in the formation of
openings in the floor of the notochordal
process, which brings the notochordal canal
into communication with the umbilical vesicle.

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• The openings rapidly become confluent and
the floor of the notochordal canal disappears;
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 infolds to form the
notochord.

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 Formation of notochord
• The proximal part of the notochordal canal
persists temporarily as the neurenteric canal,
which forms a transitory communication
between the amniotic and umbilical vesicle
cavities.
• When development of the notochord is
complete, the neurenteric canal normally
obliterates.
• The notochord becomes detached from the
endoderm of the umbilical vesicle, which
again becomes a continuous layer.

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 Molecular regulators of notochord
formation
• Wnt signaling pathway induction of notochord via
dorsal mesoderm expression of Wnt ligands.
• BMP signaling inhibition by noggin, chordin, and
follistatin, preventing BMP ligand interaction with
receptors.
• Essential transcription factors: goosecoid
(homeobox-containing) for organizer region
induction, brachyury (T-box) for notochordal cell
differentiation.

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 Molecular regulators of notochord
formation
• Hedgehog signaling involved in notochord
patterning along anterior-posterior axis, with
Sonic hedgehog (Shh) expression critical for
molecular identity establishment.
• Notochord's unique extracellular matrix (ECM)
secretion crucial for maintaining its structure
and function

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 As an inducer
• One of the key roles of the notochord as an
inducer is in the induction of the neural tube,
which gives rise to the central nervous system.
• The notochord secretes a number of signaling
molecules, including Sonic hedgehog (Shh)
and Noggin, that are essential for the
induction and patterning of the neural tube.

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 As an inducer
• The notochord also plays a critical role in the
induction of the somites, which give rise to the
muscles, vertebrae, and other structures.
• The notochord secretes a number of signaling
molecules, including FGF and Wnt, that are involved
in the induction and patterning of the somites.
• The notochord induces the formation of the
vertebral bodies and intervertebral discs, which form
the basis of the vertebral column.

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3/2/2024 Free template from [Link] 28
 Formation of Notochord

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 Regions with only ectoderm-endoderm
• Buccopharyn
geal
membrane-
cephalic end
• Cloacal
membrane-
caudal end
• In the median
plane where
notochord is
present

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 ALLANTOIS
• Diverticulum
formed from
posterior wall
of yolk sac
that extend to
connecting
stalk when
claocal
membrane is
formed

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 •
Establishment of body axis
Establishment of body axes occurs early in embryogenesis,
with the anterior-posterior and dorso-ventral axes specified
prior to the left-right axis, likely initiated during the morula
stage.
• During blastocyst stage, A-P axis determined, AVE cells at the
cranial end of the endoderm layer of the bi-laminar disc
migrate cranially.
• Node and primitive streak express genes regulating
craniocaudal and dorsoventral axes.
• Cranial cells of AVE express OTX2, LIM1, HESX1, cerberus, and
lefty 1, for head development and inhibiting Nodal.
• NODAL upregulates genes for dorsal/ventral mesoderm and
head/tail structures and initiates and maintains the integrity
of the node and streak.

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 Establishment of body axis
• BMP-4, with FGF, ventralizes mesoderm into
intermediate and lateral plate structures.
• Goosecoid producing chordin and with noggin and
follistatin antagonizes BMP-4, dorsalizing mesoderm into
notochord and paraxial mesoderm for the head region.
• Brachyury T antagonizes BMP-4 for dorsalization in
caudal regions forming notochord and paraxial
mesoderm.
• Absence of Brachyury T results in shortening of the
embryonic axis (caudal dysgenesis).
• The degree of shortening depends on the time at which
the protein becomes deficient.

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 Left right sidedness
• FGF-8 from node/streak induces Nodal/Lefty-2 on left,
upregulating PITX2 for left-sidedness.
• Lefty-1 on left neural tube floor plate acts as barrier against
right-sided signals.
• Sonic hedgehog (SHH) may act similarly, also repressing
right-sided gene expression.
• Brachyury(T) from notochord is essential for
Nodal/Lefty-1/Lefty-2 expression.

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 Left right sidedness
• Serotonin concentration on left restricts NODAL expression on
left side via MAD3.
• Midline genes like SHH, LEFTY1, ZIC3 establish midline and
prevent NODAL crossing over.
• Nodal in left mesoderm triggers cascade, upregulating LEFTY2
to enhance PITX2.
• PITX2, a master gene, establishes left-sidedness in heart,
stomach, and gut.
• Ectopic PITX2 expression on right leads to situs inversus,
dextrocardia.
• 5-HT neurotransmitter, concentrated on left, activates MAD3,
restricting Nodal signaling to left side.

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 Situs inversus
• It is a condition in which transposition of the viscera
in the thorax and abdomen occurs
• 20% of patients with complete situs inversus also
have bronchiectasis and chronic sinusitis because of
abnormal cilia (Kartagener syndrome).
• cilia are normally present on the ventral surface of
the primitive node and may be involved in left-right
patterning during gastrulation.

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 laterality sequences.
• Patients with these conditions do not have
complete situs inversus but appear to be
predominantly bilaterally left sided or right
sided.
• those with left-sided bilaterality have
polysplenia.
• those with right-sided bilaterality have
asplenia or hypoplastic spleen.
• Associated with heart defects

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 Situs inversus
• Altering 5-HT signaling in animal studies leads to situs inversus,
dextrocardia, and heterotaxy in humans.
• Children born to mothers who take SSRIs like Prozac, Paxil, Zoloft,
etc., have an increased risk of heart malformations and other birth
defects, supporting serotonin's role in establishing laterality.
• SNAIL transcription factor regulates right-sided development
through effector genes.
• Initiation of the cascade on the left involves mechanisms like ciliary
motion in node to create a gradient of Nodal toward the left or
signaling gradients.
• Nodal plays a key role in primitive streak initiation and
maintenance.

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 Situs inversus
• HNF-3 beta maintains the node and induces regional
specificity in forebrain and midbrain areas.
• Lack of HNF-3beta leads to improper gastrulation and absence
of forebrain and midbrain structures.
• GOOSECOID activates BMP4 inhibitors, contributing to head
development regulation.
• Over or underexpression of GOOSECOID in animals results in
severe head malformations.
• Malformations include duplications similar to some conjoined
twins.
• Right-sided development genes are less defined compared to
left-sided ones.

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 Sirenmelia or caudal agenesis
• insufficient mesoderm is
formed in the caudal-most
region of the embryo
• this mesoderm contributes
to formation of
• the lower limbs,
• urogenital system
(intermediate mesoderm),
• lumbosacral vertebrae

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• Affected individuals exhibit a variable range of defects
• hypoplasia and fusion of the lower limbs,
• vertebral abnormalities,
• renal agenesis,
• imperforate anus,
• anomalies of the genital organs
• In humans, the condition is associated with maternal diabetes
and other causes

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 Terms related to laterality
• Situs solitus: Normal positioning of internal
organs.
• Situs inversus: Reversed positioning of all
organs in a mirror image arrangement.
• Situs ambiguous or heterotaxy: Discordant
organ positioning with respect to symmetry or
Isomerisms e.g. when both atria in the heart
look the same or Inversions e.g. When the
two ventricles in the heart are reversed.
 Heterotaxy
• Patients with situs ambiguous (heterotaxy)
have a high risk of other birth defects,
including midline malformations such as:
– Neural tube defects
– Cleft palate
– Anal atresia
• Around 90% of individuals with situs
ambiguous also have complex congenital heart
defects.
• The heart exhibits more laterality than most organs,
potentially explaining its increased susceptibility when
the left-right (L-R) signaling pathway is disrupted.
• Mutations in the zinc finger transcription factor ZiC3, a
gene located on the X chromosome, can cause X-linked
heterotaxy.
• Individuals with X-linked heterotaxy may have a variety
of birth defects, including:
– Neural tube defects
– Limb abnormalities
– Omphalocele
• Most individuals with X-linked heterotaxy also
have severe heart malformations.
• The association between laterality and midline
defects suggests that signaling pathways
establishing the anterior-posterior (A-P) and
left-right (L-R) axes must interact to specify the
correct positioning of the body's organs and
other structures.
 THIRD WEEK OF DEVELOPMENT
• Germ cells differentiate into ectoderm,
mesoderm, endoderm
• Highly sensitive stage for teratogenic insults

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 Teratogenesis Associated With
Gastrulation
• High doses of alcohol at gastrula stage kill cells in the anterior
midline of the germ disc, producing a deficiency of the midline
in craniofacial structures and resulting in holoprosencephaly.
• In such a child, the forebrain is small,
• the two lateral ventricles often merge into a single ventricle,
and the eyes are close together (hypotelorism).
• Because this stage is reached 2 weeks after fertilization, it is
approximately 4 weeks from the last menses.
• Therefore, the woman may not recognize she is pregnant,
having assumed that menstruation is late and will begin
shortly.

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 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 and prechordal plate
• 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
• 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]

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 Growth of embryonic disc
• By the end of the third week, three basic germ layers,
consisting of ectoderm, mesoderm, and endoderm, are
established in the head region.
• the process continues to produce these germ layers for more
caudal areas of the embryo until the end of the 4th week.
• Tissue and organ differentiation has begun, and it occurs in a
cephalocaudal direction as gastrulation continues.
• Initially round later becomes broader at cephalic end and
narrow at caudal end

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 DEVELOPMENT of TROPHOBLAST
• PRIMARY VILLUS • CYTO, SYNCYTIO

• SECONDARY VILLUS • CYTO , SYNCYTIO,

MESODERMAL CORE

• TERTIARY VILLUS • CYTO, SYNCYTIO,

ENDOTHELIUM OF BV

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 Development of Chorionic Villi in Placenta

3/2/2024 Free template from [Link] 59

 DEVELOPMENT OF
TROPHOBLAST

• Formation of
OUTER
CYTOTROPHOBL
ASTIC SHELL
(anchoring or
stem villi) –
attaches the
chorionic sac
firmly to decidua

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 DEVELOPMENT OF TROPHOBLAST
• Cytotrophoblastic cells in villi progressively penetrate
the syncytium until reaching the maternal
endometrium, forming an outer cytotrophoblast shell.
• This shell surrounds the trophoblast entirely, firmly
attaching the chorionic sac to maternal endometrial
tissue.
• Villi extending from the chorionic plate to the decidua
basalis are stem or anchoring villi; those branching
from stem villi are free (terminal) villi for nutrient
exchange.
• Chorionic cavity becomes larger
• Narrowing of connecting stalk by 19-20 days

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 Fate of the Primitive Streak
• The primitive streak actively forms mesoderm by the
ingression of cells 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.
• Normally the primitive streak undergoes
degenerative changes and disappears by the end of
the fourth week.

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 Heart Primordium
• Mesenchymal cells from the primitive streak
and notochordal process migrate laterally and
cranially, between the ectoderm and
endoderm until they reach the margins of the
embryonic disc.
• These cells are continuous with the
extraembryonic mesoderm covering the
amnion and umbilical vesicle.

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• Some mesenchymal cells from the primitive
streak that have mesodermal fates migrate
cranially on each side of the notochordal
process and around the prechordal plate.
• Here they meet cranially to form cardiogenic
mesoderm in the cardiogenic area where the
heart primordium begins to develop at the
end of the third week.

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 Learning objectives
• Describe the Formation of neural tube from neural plate.
• Justify embryologically the clinical picture seen in various
neural tube defects
• Describe the process of Migration of neural crest cells
• Enlist the Derivatives of neural tube and describe the
fate of each
• Enlist the Derivatives of neural crest cells
• Enlist the ectodermal derivatives
• Describe the molecular and genetic factors for the
process of neurulation
• Describe important Neural tube defects

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 Neurulation

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 Neurulation
• The processes involved in the formation of the
neural plate and neural folds and closure of
the folds to form the neural tube constitute
neurulation.
• These processes are completed by the end of
the fourth week, when closure of the caudal
neuropore occurs.
• During neurulation, the embryo may be
referred to as a neurula.

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 Mechanism of neurulation
• It is the notochord and paraxial mesenchyme
that induce the overlying ectoderm to
differentiate into the neural plate.
• Signaling molecules involve members of the
transforming growth factor β family, Shh, and
BMPs.

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 Mechanism of neurulation
• Upregulation of (FGF) signaling together with
inhibition of the activity of bone
morphogenetic protein 4 (BMP4) causes
induction of the neural plate
• FGF increases NOGGIN and CHORDIN and
inhibits BMP4
• If ectoderm is protected from exposure to
BMPs, its “default State” is to become neural
tissue

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 Mechanism of neurulation
• noggin, chordin, and follistatin secreted by primitive node,
notochord, and prechordal mesoderm, inactivates BMP.
• They neuralize ectoderm by inhibiting BMP and cause
mesoderm to become notochord and paraxial mesoderm
(dorsalizes mesoderm); however, these neural inducers induce
only forebrain and midbrain types of tissues.
• Induction of caudal neural plate structures (hindbrain and
spinal cord) depends on two secreted proteins, WNT3a and
FGF

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 Neurulation
• Under the induction of notochord the
ectoderm located at or adjacent to midline
start thickening forming the neural plate
• The ectoderm of the neural plate
(neuroectoderm) gives rise to the CNS-the
brain and spinal cord. Neuroectoderm also
gives rise to various other structures, for
example, the retina.

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 Neurulation
• At first, the elongated neural plate corresponds in
length to the underlying notochord.
• It appears rostral to the primitive node and dorsal to
the notochord and the mesoderm adjacent to it.
• As the notochord elongates, the neural plate
broadens and eventually extends cranially as far as
the oropharyngeal membrane.
• Eventually the neural plate extends beyond the
notochord.

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• On approximately the 18th day, the neural plate invaginates
along its central axis to form a longitudinal median neural
groove, which has neural folds on each side.
• The neural folds become particularly prominent at the cranial
end of the embryo and 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.
• The neural tube soon separates from the surface ectoderm as
the neural folds meet.

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• Neural crest cells undergo an epithelial to
mesenchymal transition
• migrate away as the neural folds meet and the free
edges of the surface ectoderm (non-neural
ectoderm) fuse so that this layer becomes
continuous over the neural tube and the back of the
embryo.
• Subsequently, the surface ectoderm differentiates
into the epidermis.
• Neurulation is completed during the fourth week.
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• As the neural folds fuse to form the neural tube,
• some neuroectodermal cells lying along the inner margin of
each neural fold lose their epithelial affinities and
attachments to neighboring cells .
• As the neural tube separates from the surface ectoderm,
neural crest cells form a flattened irregular mass, the neural
crest, between the neural tube and the overlying surface
ectoderm.
• The neural crest soon separates into right and left parts that
shift to the dorsolateral aspects of the neural tube;
• here they give rise to the sensory ganglia of the spinal and
cranial nerves.
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• Neural crest cells subsequently move both into and over the surface of
somites.
• Although these cells are difficult to identify, special tracer techniques have
revealed that neural crest cells disseminate widely but usually along
predefined pathways.
• Neural crest cells give rise to
• the spinal ganglia (dorsal root ganglia) and the ganglia of the autonomic
nervous system.
• The ganglia of cranial nerves V, VII, IX, and X partly derived from neural
crest cells.
• Schwann cells
• leptomeninges.
• pigment cells,
• the suprarenal (adrenal) medulla, and
• many connective tissue components in the head. 80
• Laboratory studies indicate that cell
interactions both within the surface
epithelium and between it and underlying
mesoderm are required to establish the
boundaries of the neural plate
• specify the sites where
epithelial-mesenchymal transformation will
occur.

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 Migration of neural crest cells
• Neural crest cells dissociate from neuroectoderm during
neural fold elevation and fusion.
• They undergo epithelial-to-mesenchymal transition and
actively migrate into mesoderm.
• Trunk crest cells migrate after closure of the neural tube 1)
dorsally through dermis where they will enter the ectoderm
through holes in the basal lamina to form melanocytes in the
skin and hair follicles, or 2) ventrally through anterior part of
somites.
• Ventral pathway results in sensory ganglia, sympathetic and
enteric neurons, Schwann cells, and adrenal medulla.

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 Migration of neural crest cells
• Neural crest cells also form and migrate from cranial neural
folds, leaving the neural tube before closure in this region
• Cranial neural fold crest cells contribute to craniofacial
skeleton and neurons for cranial ganglia.
• They also form glial cells, melanocytes, and other cell types.
• Neural crest cells are considered the "fourth germ layer."
• Evolutionarily crucial, they expanded vertebrate diversity with
predatory adaptations.

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 NTDs
• Neural tube defects (NTDs) result when neural
tube closure fails to occur.
• If the neural tube fails to close in the cranial
region, then most of the brain fails to form,
and the defect is called anencephaly.
• If closure fails anywhere from the cervical
region caudally, then the defect is called spina
bifida,

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 NTDs
• The most common site for spina bifida to occur is in
the lumbosacral region, suggesting that the closure
process in this area may be more susceptible to
genetic and/or environmental factors.
• Anencephaly is a lethal defect, and most of these
cases are diagnosed prenatally and the pregnancies
terminated.
• Children with spina bifida lose a degree of
neurological function based on the spinal cord level
of the lesion and its severity.
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 Learning objectives
• Describe the Differentiation of mesoderm into
its constituting components
• Describe the Somite formation and its fate
• Describe the Estimation of age by somites
• Describe the formation of intra-embryonic
coelom

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 DEVELOPMENT OF SOMITES
• In addition to the notochord, cells derived from the
primitive node form paraxial mesoderm.
• Close to the node, this population appears as a thick,
longitudinal column of cells .
• Each column is continuous laterally with the
intermediate mesoderm, which gradually thins into a
layer of lateral mesoderm.
• The lateral mesoderm is continuous with the
extraembryonic mesoderm covering the umbilical
vesicle and amnion.
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 Formation of somites
• Toward the end of the third week, the paraxial mesoderm differentiates,
condenses, and begins to divide into paired cuboidal bodies, the somites
(Gr. soma, body), which form in a craniocaudal sequence.
• These blocks of mesoderm are located on each side of the developing
neural tube .
• About 38 pairs of somites form during the somite period of human
development (days 20 to 30).
• By the end of the fifth week, 42 to 44 pairs of somites are present.
• The somites form distinct surface elevations on the embryo and are
somewhat triangular in transverse section
• Because the somites are so prominent during the fourth and fifth weeks,
they are used as one of several criteria for determining an embryo's age.

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 Formation of somites
• 1st appear in future occipital region
• Develop craniocaudally
• Give rise to axial skeleton,associated muscles
and associated dermis
• 1st pair in 3rd week
• Cranial somites are the oldest and caudal the
youngest
• Motor axons from spinal cord innervates the
muscles in somites
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 Molecular regulation of somites
• Experimental studies indicate that formation
of somites from the paraxial mesoderm
involves the expression of Notch pathway
genes (Notch signaling), Hox genes, and other
signaling factors responsible for the orderly
sequencing of somites.

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• Moreover, somite formation from paraxial
mesoderm is preceded by expression of the
forkhead transcription factors Fox C1 and C2
and the craniocaudal segmental pattern of the
somites is regulated by the Delta-Notch
signaling system. A hypothetical molecular
oscillator or clock has been proposed as the
mechanism

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 Somites

• First appear in the future occipital region

• Soon develop craniocaudally

• Gives rise to the axial skeleton and associated

musculature

• Also forms adjacent dermis of the skin

• The first pair of somites appear at the end of 3rd

week
 Somites

• First appear at a short distance caudal to the

cranial end of the notochord

• Subsequent pairs form in a craniocaudal

sequence
• Immediately after segmentation the somitomeres
undergo a process of epithelialization
• form a ball of epithelial cells with a small cavity in
the centre
• The ventral region of each somite then becomes
mesenchymal again and forms the sclerotome the
bone forming cells for vertebrae and ribs
• Cells in the upper region of somites form the
dermatome and two muscle forming areas at the
ventrolateral and dorsomedial lips or edges
• Cells from these two areas migrate and proliferate to
form the progenitor muscle cells ventral to the
dermatome thereby forming the dermomyotome
• Some cells in ventrolateral region also migrate into
the adjacent parietal layer of the lateral plate
mesoderm.
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 Age determination from somites
• 1st pair in occipital region at 20th day
• From here, new somites appear in craniocaudal sequence at a
rate of approximately three pairs per day until, at the end of
the fifth week, 42 to 44 pairs are present
• There are 4 occipital, 8 cervical, 12 thoracic, 5 lumbar, 5
sacral, and 8 to 10 coccygeal pairs.
• The first occipital and the last five to seven coccygeal somites
later disappear, while the remaining somites form the axial
skeleton
• somites can be counted to determine the age of embryo
during this early time

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 INTERMEDIATE MESODERM
• Excretory units of the urinary system and the
gonads develop from this partly segmented,
partly unsegmented intermediate mesoderm
 DEVELOPMENT OF THE INTRAEMBRYONIC COELOM

• The primordium of the intraembryonic coelom

(embryonic body cavity) appears as isolated
coelomic spaces in the lateral mesoderm and
cardiogenic (heart-forming) mesoderm.
• These spaces soon coalesce to form a single
horseshoe-shaped cavity, the intraembryonic
coelom
• this divides the lateral mesoderm into two
layers
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• A somatic or parietal layer
• A splanchnic or visceral layer of lateral
mesoderm
• The somatic mesoderm and overlying
embryonic ectoderm form the embryonic
body wall or somatopleure.
• the splanchnic mesoderm and underlying
embryonic endoderm form the embryonic gut
or splanchnopleure.
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• During the second month, the intraembryonic
coelom is divided into three body cavities:
• Pericardial cavity
• Pleural cavities
• Peritoneal cavity

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• Describe the processes of vasculogenesis &
angiogenesis
• Explain the features of primordial
cardiovascular system
• Describe the anatomical justification for
Capillary hemangiomas

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 Formation of cvs
• At the end of the second week, embryonic nutrition is
obtained from the maternal blood by diffusion through the
extraembryonic coelom (chorionic cavity) and umbilical
vesicle(yolk sac).
• At the beginning of the third week, vasculogenesis and
angiogenesis (Gr. angeion, vessel + genesis, production), or
blood vessel formation, begins in the extraembryonic
mesoderm of the umbilical vesicle, connecting stalk, and
chorion .
• Embryonic blood vessels begin to develop approximately 2
days later.

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• The early formation of the cardiovascular system is
correlated with the urgent need for blood vessels to
bring oxygen and nourishment to the embryo from
the maternal circulation through the placenta.
• During the third week, a primordial uteroplacental
circulation develops .

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• The formation of the embryonic vascular system
involves two processes: vasculogenesis and
angiogenesis.
• Vasculogenesis is the formation of new vascular
channels by assembly of individual cell precursors
called angioblasts.
• Angiogenesis is the formation of new vessels by
budding and branching from preexisting vessels.

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 vasculogenesis in the embryo and extraembryonic
membranes in the third week.

• Mesenchymal cells differentiate into

endothelial precursors called Angioblast
• Angioblast aggregate to form isolated
angiogenic cell clusters or blood islands
• Small cavities appear within the blood islands
• Angioblasts flatten to form endothelial cells

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• Endothelial cells arrange themselves around
the cavities in blood island to form the
endothelium
• These endothelium lined cavities soon fuse to
form networks of endothelial channels called
Vasculogenesis
• Vessels sprout into adjacent areas by
endothelial budding and fuse with other
vessels called Angiogenesis
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• Blood cells develop from the endothelial cells of
vessels called hemangioblasts
• Develop at the end of 3rd week on the yolk sac and
allantois
• Hematogenesis does not begin until 5th week
• It occurs first along the aorta
• then in liver and later in spleen, bone marrow &
lymph nodes

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• Fetal and adult erythrocytes are derived from
different hematopoietic progenitor cells
(hemangioblasts).
• The mesenchymal cells surrounding the
primordial endothelial blood vessels
differentiate into the muscular and connective
tissue elements of the vessels.

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 The Primordial Cardiovascular
System
• Heart & great vessels develop from mesenchymal
cells in the cardiogenic area
• Paired longitudinal endothelial lined channels or
endocardial heart tubes develop during the 3rd week
• These tubes fuse to form the heart tube
• The tubular heart joins with blood vessels in the
embryo, connecting stalk, chorion, and umbilical
vesicle to form a primordial cardiovascular system .

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 • By the end of the third week, the blood is
circulating and the heart begins to beat on
the 21st or 22nd day.
• The cardiovascular system is the first organ
system to reach a functional state.
• The embryonic heartbeat can be detected
using Doppler ultrasonography during the
fifth week, (approx.7 weeks after LMP).

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 Capillary Hemangioma
• Capillary hemangiomas are the most common tumors of infancy, occurring
in approximately 10% of all births.
• They are abnormally dense collections of capillary blood vessels.
• These tumors can occur anywhere but are often associated with
craniofacial structures.
• Facial lesions may be focal or diffuse, with diffuse lesions causing more
secondary complications such as ulcerations, scarring, and airway
obstruction.
• INSULIN-LIKE GROWTH FACTOR 2 (IGF-2) is highly expressed in these
lesions and may contribute to abnormal vessel growth.
• The role of Vascular Endothelial Growth Factor (VEGF) in capillary
hemangiomas has not been determined definitively.

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 rd
HIGHLIGHTS of 3 Week of
Development
• Gastrulation ( 3 germ layers established)
• Formation of notochord and allantois
• Embryonic disc becomes elongated with buccopharyngeal membrane
rostrally and cloacal membrane caudally
• 3 layers of trophoblast- Formation of secondary and tertiary villi
cytotrophoblast, syncytiotrophoblast, endothelial lining of blood vessels
• Formation of outer cytotrophoblastic shell
• Beginning of neurulation
• Start of somite formation
• Development of primordium of the intraembryonic coelom (embryonic
body cavity)
• Heart begins to beat and blood starts circulating

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 Abnormal Growth of Trophoblast
• The main mechanisms for development of complete
hydatidiform moles are
• Fertilization of an empty oocyte by a sperm, followed
by duplication (monospermic mole)
• Fertilization of an empty oocyte by two sperms
(dispermic mole)
• A complete (monospermic) hydatidiform mole
results from fertilization of an oocyte in which the
female pronucleus is absent or inactive-an empty
oocyte.
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• A partial (dispermic) hydatidiform mole
usually results from fertilization of an oocyte
by two sperms (dispermy).
• Most complete hydatidiform moles are
monospermic.
• For both types, the genetic origin of the
nuclear DNA is paternal.

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 Allantoic Cysts
• Allantoic cysts, remnants of the extraembryonic
portion of the allantois, are usually found between
the fetal umbilical vessels and can be detected by
ultrasonography.
• most commonly detected in the proximal part of the
umbilical cord, near its attachment to the anterior
abdominal wall.
• asymptomatic until childhood or adolescence, when
they may present with infection and inflammation.

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 Derivatives of mesoderm
• Connective tissue
• Cartilage
• Bone
• Striated & smooth muscles
• Heart
• Blood & lymphatic vessels
• Kidneys, ovaries, testes & genital ducts
• Serous membrane lining the body cavities
• Spleen & cortex of the supra renal gland

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 Ectoderm
• Surface ectoderm
• Neuroectoderm
Surface Ectoderm Derivatives
• Epidermis of the skin
• Hair
• Nail
• Sweat & Sebaceous glands
• Mammary glands
• Enamel of the teeth
• Lens of eye
• Internal ear
• Anterior lobe of the pituitary gland
 Neuroectoderm
• Neural Tube
• Neural Crest Cells
 ectoderm Derivatives
• Central nervous system
• Peripheral nervous system
• Retina
• Sensory epithelia of nose & ear
• Pineal gland
• Posterior lobe of the pituitary gland
• The epidermis, including the hair and nails
• ■ The subcutaneous glands
• ■ The mammary glands
Neural Crest Cells Derivatives
• Sensory ganglia (cranial & spinal)
• Autonomic ganglia
• Meninges (Pia mater & Arachnoid mater) of
the brain & spinal cord
• Schwann cells
• Satellite cells
• Melanoblasts
• Suprarenal medulla (chromaffin cells)
• Several skeletal & muscular components in
the head (derived from pharyngeal arches)
• Connective tissue and bones of the face and
skull
• Dermis in face and neck
• C cells of the thyroid gland
• Conotruncal septum in the heart
• Odontoblasts
• Glial cells

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 Process of migration of Neural
crest cells
• epithelial-to-mesenchymal transition as it leaves the
neuroectoderm by active migration and displacement to enter
the underlying mesoderm
• Crest cells from the trunk region migrate along one of two
pathways:
• (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

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 Process of migration of Neural
crest cells
• Neural crest cells also form and migrate from cranial neural
folds, leaving the neural tube before closure in this region.
• These cells contribute to the craniofacial skeleton as well as
neurons for cranial ganglia, glial cells, melanocytes, and other
cell types
• Differentiation and migration of neural crest cells are
regulated by molecular interactions of specific genes (e.g.,
FoxD3, Snail2, Sox9, and Sox10), signaling molecules, and
transcription factors.

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 Derivatives of Endoderm
Endoderm gives rise to the epithelial lining of:

• Trachea

• Bronchi

• lungs
 Derivatives of Endoderm
Endoderm gives rise to the epithelial lining of:

• Gastrointestinal tract

• Liver

• Pancreas

• Urinary bladder

• urachus
 Derivatives of Endoderm
Endoderm gives rise to the epithelial lining of:

• Pharynx
• thymus
• Thyroid
• Tympanic cavity
• Pharyngotympanic tube
• Tonsils
• Parathyroid glands
 Formation of Gut

• Primordial gut at the beginning of the 4th week

is closed at its:

• Cranial end by oropharyngeal membrane

• Caudal end by the cloacal membrane

 Formation of Gut

• Primordial gut forms during the 4th week as

the head, tail and lateral fold incorporate the
dorsal part of the yolk sac into the embryo

• The endoderm of the primordial gut gives rise

to most of the epithelium and glands of the
digestive tract