are referenced to The Developing Human, Clinically Oriented
Embryology, 8th ed. by Moore and Persaud, 2008, Saunders.
EARLY EMBRYOLOGY: SOMITE STAGE
AND LIMB BUDS
- Week 1-2: formation of zygote, implantation and formation
of bilaminar embryo (p. 3-4, fig. 1-1).
- Weeks 3-8: Embryological period (p. 4-5, fig. 1-1).
- Weeks 9-38: Fetal period (p. 5-6, figs. 1-1 and 1-2).
DEVELOPMENT OF THE SOMITES (week 3)
The intraembryonic mesoderm on each side of the forming
notochord and neural tube thickens to form a longitudinal
column of paraxial mesoderm. By the end of the 3rd week, the paraxial
mesoderm divides into paired bodies called somites, located bilaterally
of the neural tube (p. 64, fig. 4-10).
- The somites give rise to the axial skeleton (vertebrae,
ribs), associated musculature and adjacent dermis of skin.
- The first pair of somites develop a short distance posterior
to the cranial end of the notochord, and the rest of the somites form caudally.
Around 38 pairs of somites form during the somite period of development,
from days 20 to 30. The final number is 42 to 44 pairs. The somites may
be used as a criterion to determine the age of the embryo (p. 81-89).
- A cavity, the mycocoele, forms within each somite
- Each somite becomes differentiated into ventromedial
sclerotome (for vertebrae and ribs), myotome (muscles) and dermatome
(skin; p. 340, fig. 14-1).
- At the beginning of the 4th week, the somites (4) are
well formed and the neural tube is also formed but it is opened at the
rostral and caudal neuropores (p. 81,
- Upper limb buds become recognizable during week 4 (day
26 or 27) and the lower limb buds become present by the end of week 4 (day
28; p. 84, fig. 5.12). The patterning of the limb development is
regulated by Homeobox-containing (Hox) genes.
- The upper limb buds appear low on the embryo due to the
dominant development of the head and neck.
- The upper limb buds form opposite the caudal cervical
segments and lower limb buds form opposite the lumbar and upper sacral
Limb bud (p. 366, fig. 16-2)
Each limb bud consists of a mass of mesenchyme derived
from the somatic mesoderm, covered by a layer of ectoderm.
At the tip of each limb bud, ectodermal cells form an apical ectodermal
ridge, which promotes growth and development of the limbs in the proximo-distal
axis . Fibroblast growth factors and T-box genes (tbx-4
and tbx-5) from the apical ectodermal ridge activate the mesenchymal cells at the posterior margin of the
limb bud (the zone of polarizing activity). This causes expression of the
Sonic Hedgehog gene, which controls the patterning of the limb along the
anterior-posterior axis. Expression of Wnt7 from the dorsal epidermis of
the limb bud and engrailed-1 (EN-1) from the ventral aspect specifies the
- Bones appear during week 5 as mesenchymal condensations
in the limb buds (p. 371, fig. 16-7)
- Upper limbs show regional differentiation with developing
hand plates (p. 367, fig. 16-3).
Week 6 (p. 354, fig. 14-14; p. 371, fig.
- Mesenchymal models of the bones in the limbs undergo
chondrification to form hyaline cartilage.
- The clavicle develops by intramembranous ossification
and later develops articular cartilages.
- The cartilage models form sooner in the upper limb than
in the lower limb and in a proximodistal sequence.
Further differentiation of the limb buds during week 6
(p. 367, fig. 16-3):
- Identifiable elbow and wrists regions are formed.
- Hand plates develop ridges, called digital rays
and these will become the future thumb and fingers. At the tip of each
digital ray is a portion of the apical ectodermal ridge. It induces development
of the mesenchyme into the primordia of bones. Areas between the rays contain
- Development of the lower limb buds is always slower by
a few days.
- Loose mesenchyme between the digital rays break down
and notches appear between the digital rays in the hand plates.
- Digital rays form in the foot plate.
- Ossification in the long
bones begin by the end of the embryonic period (week 7). The primary centers
are in the diaphyses (p. 343, fig. 14-5).
- Limb muscles are
formed by myogenic precursor cells that migrate into the limb buds and
differentiate into myoblasts. They are
derived from the dorsolateral muscle-forming region of the somites, an area
which expresses the muscle-specific genes MyoD
Expression of MyoD results from the influence of
activating Wnt proteins and inhibitory BMP-4 protein. The myoblasts
form a muscle mass which divides into a dorsal (extensor) and ventral
Limb rotation begins (p. 373, fig. 16-9):
- Originally, the flexor aspect of the limbs is ventral
and the extensor aspect is dorsal; the preaxial border is cranial and the
postaxial border is caudal in direction.
- The upper limbs rotate 90 degrees on their longitudinal
axis. Elbows point posteriorly and extensor muscles now lie lateral and
- The lower limbs rotate 90 degrees in the opposite direction
of rotation of the upper limbs and the knees face anteriorly. The extensor
muscles now lie anteriorly.
- The radius in the forearm is homologous to the tibia
in the leg, and the ulna is homologous to the fibula.
Muscles of the limb shift their position during development
because of the lateral rotation of the upper limb and medial rotation of the
- Muscles forming on the dorsal side of
the long bones give rise to extensor and supinator muscles of the upper
limbs and extensor and abductor muscles of the lower limb. They are
innervated by the dorsal branches of the ventral primary rami.
- Muscles forming on the ventral side of the long bones
become flexor and pronator muscles of the upper limb and flexor and adductor
muscles of the lower limb. They are innervated by the ventral branches
of the ventral primary rami.
Week 8 (Last week of embryonic
life; p. 372 fig. 16.8)
At the beginning of week 8,
- The digits of the hand are short and webbed.
- Notches develop between the digital rays of the feet.
At the end of week 8, there are distinct regions in the
limbs, with long fingers and distinct toes.
FETAL PERIOD (p. 5-6,
fig. 1-1 and 1-2)
- The fetus has short legs and small thighs at the beginning
of week 9.
- By the end of week 12, the upper limbs have reached their
final relative length but the lower limbs have not.
- Primary ossification centers are present in all long
bones (p. 343, fig. 14-5).
- Order of ossification: Clavicle, femora, etc...
- Secondary ossification centers
appear in the epiphyses (p. 343, fig.
14-5). The first ones to appear are in the distal end of the femur
and the proximal end of the tibia, at the knee joint.
- The epiphyseal cartilage plate intervenes between the
diaphysis and epiphysis. When it is replaced around age 25, growth of the bones ends.
A dermatome is the area of skin innervated by a
single spinal nerve and its dorsal root ganglion (p. 373, fig. 16-10).
Development of the innervation of the limbs
- Peripheral nerves grow from the brachial and lumbar plexuses
into the mesenchyme of the limb buds during week 5.
- The distribution is segmental, supplying both dorsal
and ventral aspects.
- As the limbs elongate, the cutaneous distribution follows
and an orderly sequence can still be seen in the adult.
- There is no overlap across the axial line.
Development of the blood supply to the limbs
- Limb buds are supplied by branches of the intersegmental
arteries arising from the aorta (p. 374,
- Initially, a primary axial artery and its branches supply
the limb bud and a peripheral marginal sinus drains it.
In the upper limb,
- The primary axial artery becomes the brachial artery
in the arm and the common interosseous artery in the forearm.
- The terminal branches of the brachial artery are the
radial and ulnar arteries.
- The terminal branches of the common interosseous arteries
are the anterior and posterior interosseous arteries.
- With the formation of the digits the marginal sinus breaks
up into the dorsal venous arch. The final pattern of basilic and cephalic
veins and their tributaries then arises.
In the lower limb,
- The primary axial artery will form the profunda femoris
artery in the thigh, and the anterior and posterior tibial arteries in
Embryology of the spine and spinal cord
The AXIAL SKELETON is
formed by the :
- VERTEBRAL COLUMN
- 12 PAIRS OF RIBS
Development of the vertebral column
Precartilaginous (mesenchymal) stage
During week 4, mesenchymal cells from the sclerotome of
the somites are found in 3 main areas (The Developing Human, 8th ed.,
- around the notochord,
- surrounding the neural tube,
- in the body wall.
1. Around the notochord
Each sclerotome consists of loosely packed cells cranially
and densely packed cells caudally (The Developing Human, 8th ed., p.
- Some densely packed cells move cranially and form the
intervertebral disc. Peripheral nerves will form close to the intervertebral
- The remaining densely packed cells fuse with the loosely
arranged cells of the adjacent caudal sclerotome and form the mesenchymal
centrum of the vertebra.
- Each centrum thus develops from 2 adjacent sclerotomes
and becomes an intersegmental structure (The Developing Human,
8th ed., p. 345).
- Intersegmental arteries will come to lie on each side
of the vertebral bodies. In the thorax, the dorsal intersegmental arteries
become the intercostal arteries.
The notochord degenerates and disappears where
it is surrounded by the vertebral body.
- Between the vertebrae, the notochord expands to form
the nucleus pulposus (The Developing Human, 8th ed., p. 345).
- The nucleus pulposus is later surrounded by the circular
fibers of the anulus fibrosus.
- The nucleus pulposus and anulus fibrosus form the intervertebral
- Remnants of the notochord may persist and give rise to
a chordoma. This slow-growing neoplasm occurs most frequently at
the base of the skull and in the lumbosacral region (arrows in scans below)
2. Surrounding the neural tube
These mesenchymal cells form the vertebral arch (The
Developing Human, 8th ed., p. 345).
3. In the body wall
These mesenchymal cells form the costal processes
which develop into ribs in the thoracic region.
The cartilaginous stage
During week 6, chondrification centers appear in each
mesenchymal vertebra (The Developing Human, 8th ed., p. 346).
- The 2 centers in each centrum fuse at the end of the
embryonic period to form a cartilaginous centrum.
- At the same time, the centers in the vertebral arches
fuse with each other and with the centrum.
- The spinous and transverse processes develop from extensions
of chondrification centers in the vertebral arch.
Chondrification spreads until a cartilaginous vertebral
column is formed.
The bony stage
Ossification of the typical vertebrae begins during the
embryonic period and ends by year 25 of life.
2 (ventral and dorsal) primary ossification centers for
the centrum fuse to form one.
3 primary ossification centers at the end of the embryonic
period (The Developing Human, 8th ed., p. 346):
- in the centrum.
- in each half of the vertebral arch (Ossification is evident
around week 8).
At birth, each vertebra consists
of 3 bony parts connected by cartilage (The Developing Human, 8th ed.,
- The halves of the vertebral arch fuse during years 3-5.
- The laminae of the arch first unite in the lumbar region
and the progression moves cranially.
- The vertebral arch articulates with the centrum at cartilaginous
neurocentral joints (The Developing Human, 8th ed., p. 346).
- These articulations permit the vertebral arches to grow
as the spinal cord enlarges.
- The neurocentral joints disappear when the vertebral
arch fuses with the centrum during years 3-6.
5 secondary ossification centers appear (The Developing
Human, 8th ed., p. 346):
- tip of the spinous process.
- tip for each transverse process.
- 2 rim (annular) epiphyses: 1 superior and 1 inferior
for the vertebral body.
The vertebral body is a composite of the superior and
inferior annular epiphyses and the mass of bone between them. It includes
the centrum, parts of the vertebral arch and the facets for the heads of
All secondary centers unite with the rest of the vertebra
around year 25.
Ossification of atypical vertebrae
Exceptions to the typical ossification of vertebrae occur
in C1, C2, C7, lumbar vertebrae, sacrum and coccyx.
- 95% of the population has 7C, 12 T, 5 L and 5 S vertebrae.
- 3% have 1 or 2 more vertebrae.
- 2% have 1 less.
Examine the entire vertebral column because an apparent
extra or absent vertebra in one segment may be compensated by an absent
or extra vertebra in an adjacent segment (ex: 11T and 6 L vertebrae).
Development of the spinal cord
The nervous system develops from an area of embryonic ectoderm
called the neural plate which appears during week 3 (The Developing
Human, 8th ed., p. 382).
The underlying notochord and adjacent mesoderm induce the
formation of the neural plate. The neural tube and the neural
crest differentiate from the neural plate.
- The neural tube gives rise to the central nervous system
(brain and spinal cord; The Developing Human, 8th ed., p. 396).
- The neural crest gives rise to the peripheral nervous
system (cranial, peripheral, autonomic ganglia and nerves) and Schwann
cells, pigment cells, odontoblasts, meninges, and bones and muscles of
the head (The Developing Human, 8th ed., p. 389).
Central nervous system
- Formation of the neural tube begins during the early
part of week 4 (22-23 days) in the region of the 4th to 6th pairs of somites
(future cervical region of the spinal cord; The Developing Human, 8th ed.,
- At this stage ,the cranial 2/3 of the neural plate and
neural tube down to somites #4 represent the brain and the caudal 1/3 of
the neural tube and plate represent the spinal cord.
- Neural folds fuse and the neural tube is temporarily
open at both ends, communicating freely with the amniotic cavity.
- The rostral neuropore closes around day 25 and
caudal neuropore on day 27.
- Walls of the neural tube thicken to form the brain and
- The lumen of the neural tube is converted to the ventricular
system of the brain and the central canal of the spinal cord.
The spinal cord is formed from the neural tube caudal to
- The central canal is formed by week 9 or 10 (The Developing
Human, 8th ed., p. 382, 386, 388).
- Pseudostratified, columnar neuroepithelium in the walls
constitute the ventricular zone (ependymal layer) and give rise
to all neurons and macroglial cells (astroglia and oligodendroglia) in
the spinal cord (The Developing Human, 8th ed., p. 387).
- The outer parts of the neuroepithelial cells differentiate
into a marginal zone which will give rise to the white matter of
the spinal cord as axons grow into it from neurons in the spinal cord,
spinal ganglia and brain.
- Neuroepithelial cells in the ventricular zone differentiate
into neuroblasts and form an intermediate zone between the ventricular
and marginal zones. They will give rise to neurons.
- Glioblasts (spongioblasts) differentiate from neuroepithelial
cells after neuroblast formation has stopped. They migrate from the ventricular
zone into the intermediate and marginal zones. Some become astroblasts
and then astroglia (astrocytes). Others become oligodendroblasts
and then oligodendroglia (oligodendrocytes). The remaining neuroepithelial
cells differentiate into ependymal cells lining the central canal of the
spinal cord (The Developing Human, 8th ed., p. 386).
- Microglia are derived from the mesenchymal cells.
They invade the nervous system late in the fetal period after penetration
from blood vessels.
Proliferation and differentiation of the neuroepithelial
cells in the developing spinal cord produce thick walls and thin roof and
floor plates. A shallow longitudinal sulcus limitans appears in the
lateral walls of the spinal cord and separates the dorsal alar plate
from the ventral basal plate (The Developing Human, 8th ed., p. 386).
- Alar plates: cells form the dorsal horns and will
have afferent functions.
- Basal plates: cells form the ventral and lateral horns
and will have efferent functions. Axons grow out of the spinal cord
to form the ventral roots.
- The dorsal root ganglia are formed from the neural
crest cells. Their axons enter the spinal cord and form the dorsal
Mesenchyme surrounding the neural tube condenses to form
the primitive meninx.
- The outer layer thickens to form the dura mater.
- The inner layer remains thin and forms the pia-arachnoid.
Positional changes of the developing spinal cord
In the embryo, the spinal cord extends the entire length
of the vertebral canal and the spinal nerves pass through the intervertebral
foramina near their levels of origin.
This relationship does not persist because the spine and
the dura mater grow more rapidly than the spinal cord. The caudal end of
the spinal cord comes to lie at relatively higher levels.
Positional changes of the developing spinal cord (The
Developing Human, 8th ed., p. 390)
- At month 6 of gestation, the end of the spinal cord lies
at the level of S1.
- In the newborn infant, it lies at L 3
- In the adult, it lies at L 2-3. Lumbar and sacral spinal
nerve roots run obliquely from the spinal cord to their corresponding intervertebral
- are mostly due to the defective closure of the caudal
neuropore at the end of week 4. The defects will involve the tissue overlying
the spinal cord (meninges, vertebral arch, dorsal muscles and skin).
- involving the spinal cord and vertebral arches are called
spina bifida (nonfusion of the vertebral arches; The Developing Human,
8th ed., p. 391)
Spina bifida occulta (The
Developing Human, 8th ed., p. 391, 392 fig. 17-14)
- is a defect in the vertebral arch (neural arch) resulting
from failure of the halves of the vertebral arch to grow normally and fuse
in the median plane.
- occurs at L 5 or S 1 vertebra in about 10% of the population.
- may only be evident as a small dimple with a tuft of
- produces no clinical symptoms although a small percentage
may have significant defects of the underlying spinal cord and spinal roots.
Spinal dermal sinus
- representing the area of closure of the caudal neuropore
at the end of week 4, may exist.
- It is the last place of separation between the ectoderm
and the neural tube.
- The dimple may be connected by a fibrous cord with the
are tumors arising from surface ectodermal cells incorporated into the neural
tube during closure of the caudal neuropore.
Spina bifida cystica (The Developing Human, 8th ed.,
- is a protrusion of the spinal cord and/or meninges through
the defective neural arch.
- is present in 1/1000 births.
- may result in loss of sensation in corresponding dermatome,
complete or partial skeletal muscle paralysis, sphincter paralysis (with
lumbar meningomyeloceles) and saddle anesthesia.
- with meningocele: only meninges and cerebrospinal fluid
in the sac.
- with meningomyelocele (The Developing Human, 8th ed.,
p. 391, 393): spinal cord and nerve roots included with meninges
and CSF in the sac, covered by skin or thin membrane. There are marked
neurological deficits inferior to the sac, due to incorporation of the
neural tissue into the wall of the sac (This usually occurs in the lumbar
region and may be associated with craniolacunia or defective calvarium).
- with myeloschisis (with myelocele: open spinal cord due to failure
of neural folds to fuse. The spinal cord in this area is a flattened mass.
- cystica and/or meroanencephaly (absence of part of the
brain; (The Developing Human, 8th ed., p. 392, 395) is suspected
in utero when there is a high-level of alpha-fetoprotein in the
amniotic fluid or in the maternal blood serum.
- Amniocentesis or ultrasound should be performed at about
week 10 when the vertebral column becomes visible.
The lower respiratory system (from the pharynx down)
- develops during week 4 (26-27 days)
- starts as a median laryngotracheal groove (The
Developing Human, 8th ed., p. 200, fig. 10-3) in the caudoventral wall
of the primitive pharynx.
- The endoderm (The Developing Human, 8th ed.,
p. 201, fig. 10-4) lining the groove gives rise to the epithelium and
glands of the larynx, trachea, bronchi and the pulmonary epithelium.
- Connective tissue, cartilage and smooth muscle of these
structures develop from the splanchnic mesenchyme surrounding the
The laryngotracheal groove deepens into a diverticulum
ventrally which enlarges distally into a lung bud (The Developing Human,
8th ed., p. 200, fig. 10-2). The diverticulum becomes separated from
the primitive pharynx by longitudinal trachoesophageal folds which
fuse to form the trachoesophageal septum, dividing the foregut into
the ventral laryngotracheal tube and the dorsal esophagus.
A fistula (The Developing Human, 8th ed., p. 202, fig. 10-5,
10-6) may exist connecting trachea and esophagus
and resulting in abnormal communication between the 2.
- This is usually associated with superior esophageal
atresia. In a newborn infant, this is associated with coughing and
choking upon swallowing. Gastric contents may reflux into the trachea and
lungs resulting in pneumonia or pneumonitis (inflammation
of the lungs).
- An excess of amniotic fluid (polyhydramnios) is
associated with esophageal atresia and trachoesophageal fistula because
amniotic fluid may not pass to the stomach and intestines for absorption
and transfer via the placenta for disposal.
The lung bud develops into 2 endodermal bronchial buds
(The Developing Human, 8th ed., p. 202, fig. 10-7) which grow into
the pericardioperitoneal cavities, the primordia of the pleural cavities.
- Early in week 5, each bronchial bud enlarges into the
primordium of a primary bronchus. The right one is slightly larger
than the left and is oriented more vertically
(The Developing Human, 8th ed., p. 203, fig. 10-8.
- The primary bronchi subsequently divide into secondary
bronchi and then into the tertiary bronchi by week 7.
- By week 24, they divide another 14 times and the respiratory
bronchioles have developed.
- They will divide an additional 7 more times before birth.
- As the bronchi develop, the surrounding mesenchyme synthesizes
the surrounding cartilages, smooth muscle, connective tissue and capillaries.
PLEURAE (The Developing Human, 8th ed., p. 202, fig.
- The lungs acquire a layer of visceral pleura from the
- The thoracic body wall becomes lined by a layer of parietal
pleura derived from the somatic mesoderm.
LUNG DEVELOPMENT (The Developing Human, 8th ed., p.
204, fig. 10-9; p. 205, fig. 10-10)
1) Pseudoglandular period (5-17 weeks)
By week 17 all major elements of the lungs have formed
except for those involved with gas exchange. The lungs look like an endocrine
organ. No respiration is possible!
2) Canalicular period (16-25 weeks)
The lumen of the bronchi and terminal bronchioles become
larger and the lungs become vascularized. By week 24, respiratory bronchioles
have developed and respiration becomes possible, although the chances of
survival are slim.
3) Terminal sac period (24 weeks to birth)
- More terminal sacs develop and capillaries enter into
close relationship with them. They are lined with Type 1 alveolar cells
- Type II pneumocytes secrete
surfactant counteracting the surface tension forces and facilitating
expansions of the terminal sacs.
Surfactant reaches adequate levels 2 weeks before birth.
Adequate pulmonary vasculature and sufficient surfactant
are critical to the survival of premature infants.
4) Alveolar period (late fetal period to 8 years)
95% of the mature alveoli develop after birth. A newborn
infant has only 1/6 to 1/8 of the adult number of alveoli and the lungs
look denser in an x-ray.
Developing lungs at birth are half filled with amnotic
fluid. The fluids in the lungs are cleared:
- through mouth and nose by pressure on the thorax during
- into the pulmonary capillaries.
- into the lymphatics and pulmonary arteries and veins.
The cardiovascular system begins to develop during week
Mesenchymal cells derived from the mesoderm form endothelial
tubes which join to form the primitive vascular system (The Developing
Human, 8th ed., p. 286, fig. 13-1).
HEART DEVELOPMENT (WEEK 3)
Heart develops from splanchnic mesenchyme in the cardiogenic
Bilateral cardiogenic cords
- are formed from the mesenchyme
- become canalized
- and form the paired endocardial heart tubes (The Developing
Human, 8th ed., p. 293, fig. 13-7; p. 294 fig. 13-8). These fuse into a single heart
tube forming the primitive heart.
Surrounding mesenchyme thicken to form the myoepicardial
mantle (future myocardium and epicardium) separated from
the endothelial heart tube (future endocardium) by the gelatinous
cardiac jelly (The Developing Human, 8th ed., p. 294, fig. 13-8).
The future heart develops dilatations and constrictions
resulting in 4 chambers (The Developing Human, 8th ed., p. 296-298):
- sinus venosus
- primordial atrium
- bulbus cordis
The truncus arteriosus is continuous caudally with
the bulbus cordis, and enlarges cranially to form the aortic sac
from which the aortic arches arise (The Developing Human, 8th
ed., p. 296, fig. 13-10).
The sinus venosus receives (The Developing Human, 8th
ed., p. 296, fig. 13-10):
- the umbilical veins from the chorion.
- the vitelline veins from the yolk sac
- the common cardinal veins from the embryo.
3 systems of paired veins drain into the primitive heart:
- the vitelline system will become the portal system;
- the cardinal veins will become the caval system;
- the umbilical system which degenerates after birth
(The Developing Human, 8th ed., p. 287, 289, 290).
The bulbus cordis and the ventricle grow faster and the
heart bends upon itself, forming a bulboventricular loop (The Developing
Human, 8th ed., p. 294, fig. 13-8 E).
The atrium and sinus venosus come to lie dorsal to the
bulbus cordis, truncus arteriosus and ventricle (The Developing Human,
8th ed., p. 297).
At the same time, the heart invaginates into the pericardial
cavity (The Developing Human, 8th ed., p. 295).
The dorsal mesocardium which attaches it to the
dorsal wall of the pericardial cavity degenerates and forms the tranverse
pericardial sinus (The Developing Human, 8th ed., p. 294, fig. 13-8).
First heartbeat occurs at 21 to 22 days and originates
in the muscle, forming peristalsis-like waves beginning in the sinus venosus.
By the end of week 4 coordinated contractions of the heart
results in unidirectional flow:
- Blood enters the sinus venosus from the vitelline, cardinal
and umbilical veins (The Developing Human, 8th ed., p. 287);
- Blood flows into the primitive ventricle;
- Upon ventricular contraction, blood flows into the bulbus
cordis and the truncus arteriosus into the aortic sac, passing into the
aortic arches (The Developing Human, 8th ed., p. 287) and
- Blood then passes to the dorsal aortae for distribution
to the embryo, yolk sac and placenta.
The heart divides into 4-chambered heart between weeks
4 and 7.
1) Endocardial cushions (The Developing Human,
8th ed., p. 297-298) form on the dorsal
and ventral walls of the atrioventricular canal. At week 5, they approach
each other and fuse, dividing the atrioventricular canal into right
and left canals.
2) Atria are partitioned successively by the septum
primum and the septum secundum (The Developing Human, 8th ed., p.
299-301). The latter is an incomplete partition and leaves
a foramen ovale. The foramen ovale has a valve formed from the degeneration
of the cranial portion of the septum primum.
Before birth the foramen ovale allows blood to pass from
the right atrium into the left atrium; reflux is prevented by the valve
(The Developing Human, 8th ed., p. 301).
After birth the foramen ovale normally closes by fusion
of the septum primum and the septum secundum.
3) The sinus venosus develops a left horn which becomes
the coronary sinus (The Developing Human, 8th ed., p. 302)
and a right horn which will be incorporated into the right atrium. The smooth
part of the right atrium, the sinus venarum, is derived from the
sinus venosus whereas the muscular part, the auricle, is derived
from the primitive atrium. The 2 portions are separated internally by the
crista terminalis and externally by the sulcus terminalis.
4) The primitive pulmonary vein and its 4 main branches
become partially incorporated into the left atrium (The Developing Human,
8th ed., p. 303). This results in the 4 pulmonary veins.
The portion derived from the original left atrium retains a trabeculated
5) The ventricles become partitioned by a crescentic fold
which is open cranially until the end of week 7 (interventricular foramen;
The Developing Human, 8th ed., p. 304). The interventricular
septum is formed of a central membranous part and a surrounding muscular
part. After closure, the right ventricle communicates with the pulmonary
trunk and the left ventricle with the aorta.
6) During week 5, the bulbus cordis and the truncus arteriosus
become divided by an aorticopulmonary septum into the definitive
pulmonary trunk and aorta (The Developing Human, 8th ed., p. 307, 317). Valves develop from proliferation of the subendocardial tissue.
The primitive atrium acts as a temporary pacemaker.
But the sinus venosus soon takes over.
- The sinuatrial (SA) node develops during week
5. It is part of the sinus venosus which becomes incorporated into the
- The atrioventricular (AV) node also develops from
the cells in the wall of the sinus venosus together with cells from the
atrioventricular canal region.
The critical period of development is from day 20 to day
50 after fertilization.
Improper partitioning of the heart may result in defects
of the cardiac septa, of which the ventricular septal defects are most common
(25% of congenital heart disease).
Membranous ventricular septal defect (most common):
- involves the oval membranous portion of the interventricular
septum (The Developing Human, 8th ed., p. 304, 313) which
fails to develop.
- is due to the failure of extensions of subendocardial
tissue growing from the right side of the fused endocardial cushions and
fusing with the aorticopulmonary septum and the muscular part of the interventricular
Muscular septal defect:
- Perforation may appear anywhere in the muscular part
of the interventricular septum (multiple defects = Swiss cheese type of
ventricular septal defect) due perhaps to excessive resorption of myocardial
tissue during formation of the muscular part of the interventricular septum.
Absence of interventricular septum is rare and results
in a 3-chambered heart called cor triloculare biatriatum.
The tetralogy of Fallot consists of (The Developing
Human, 8th ed., p. 316):
- pulmonary valve stenosis:
the cusps of pulmonary valve are fused together to form a dome with a narrow
- ventricular septal defect
- overriding aorta
- hypertrophy of right ventricle
Cyanosis is an obvious sign but may not be present at
- When the branchial arches form during week 4 and 5, they
are penetrated by arteries arising from the aortic sac, which are called
the aortic arches.
- During week 6 to 8 the primitive aortic arch pattern
is transformed into the adult arterial arrangement of carotid, subclavian,
and pulmonary arteries (The Developing Human, 8th ed., p. 321).
The lymphatic system begins to develop around week 5 (The
Developing Human, 8th ed., p. 334).
- 6 primary lymph sacs develop and later become interconnected
by lymph vessels;
- lymph nodules do not appear until just before and/or
- Hygroma: tumor-like mass
of dilated lymphatic vessels derived from the pinched-off portion of the
jugular lymph sac.
FETAL CIRCULATION (The Developing Human, 8th ed., p.
- Oxygenated blood returns from the placenta by the umbilical
- Half of the blood passes through the liver whereas the
other half bypasses the liver by the ductus venosus.
- Blood enters into the inferior vena cava and then the
right atrium of the heart. This blood is now partially deoxygenated because
it is mixed with returning blood from the lower portion of the body and
the abdominal organs.
- Most of the blood in the right atrium passes through
the foramen ovale into the left atrium and mixes with the blood
returning from the lungs (deoxygenated).
- From the left atrium, blood passes into the left ventricle
and the ascending aorta. Arteries to the heart, head and neck, and upper
limbs receive well-oxygenated blood.
- A small amount of blood from the right atrium mixes with
blood from the superior vena cava and coronary sinus. It passes into the
right ventricle and leaves via the pulmonary trunk. Most of it passes into
the ductus arteriosus into the aorta. A small amount passes into
- 50% of the blood passes via the umbilical arteries into
the placenta for reoxygenation, the rest supplies the viscera and the inferior
1/2 of the body.
After birth, the foramen ovale, ductus arteriosus, ductus
venosus and umbilical vessels are no longer needed and they close (The
Developing Human, 7th ed., p. 373, fig. 14-47).
The right ventricular wall is thicker in the newborn but
by the end of month 1, the left ventricular wall is thicker.
The fetal circulation is designed to carry oxygenated blood
from the placenta to the fetal circulation, bypassing the lungs.
- Changes that will result in a normal adult circulation
occurs during infancy.
- Defects will commonly involve a patent foramen ovale
(The Developing Human, 8th ed., p. 313) and/or patent ductus
arteriosus (The Developing Human, 8th ed., p. 315, 333).
Development of the body cavities and the diaphragm
The Developing Human - Clinically Oriented Embryology - Moore and Persaud, 8th
edition - Chapter 8
The intraembryonic coelom is the primordium of the
embryonic body cavities and begins to develop near the end of week 3
(fig. 8-1). By the beginning
of week 4, it is a horseshoe-shaped cavity in the cardiogenic and lateral
The curve of the horseshoe represents the future pericardial
cavity (fig. 8-2B) and its
lateral limbs represent the future pleural and peritoneal cavities (fig. 8-2C).
During folding of the embryonic disc in week 4,
the lateral parts of the intraembryonic coelom are brought together on the
ventral aspect of the embryo (fig. 8-2F).
- When the caudal part of the ventral mesentery disappears,
the right and left parts of the intraembryonic coelom merge and form the
- As the peritoneal portions of the intraembryonic coelom
come together, the splanchnic layer of the mesoderm encloses
the primitive gut and suspends it from the dorsal body wall by a double-layered
peritoneal membrane known as the dorsal mesentery.
Until week 7, the embryonic pericardial cavity communicates
with the peritoneal cavity through paired pericadioperitoneal canals
During weeks 5 and 6, partitions form near the cranial
and caudal ends of these canals:
- Fusion of the cranial pleuropericardial membranes
with mesoderm ventral to the esophagus separates the pericardial
cavity from the pleural cavities (fig. 8-5).
- Fusion of the caudal pleuroperitoneal membranes ( fig. 8-6
& fig. 8-7), during
formation of the diaphragm, separates the pleural cavities from the peritoneal
The diaphragm forms from (figs. 8-7, 8-8 & 8-9):
1) the septum transversum,
2) the pleuroperitoneal membranes,
3) the dorsal mesentery of the esophagus,
4) the body wall.
A posterolateral defect of the diaphragm results in congenital
diaphragmatic hernia (figs.8-10, 8-11, 8-12) and is due to failure of fusion between the pleuroperitoneal membranes
and other diaphragmatic components.
Embryology of the abdominal contents
The Developing Human - Clinically Oriented Embryology - Moore and Persaud, 8th
edition - Chapter 11
The primitive gut forms during week 4 when
the embryo folds and incorporates the dorsal part of the yolk sac (fig. 11-1).
- The endoderm of the primitive gut gives rise to
the epithelial lining of most of the digestive tract, biliary passages
and parenchyma of liver and pancreas.
- The epithelium of the cranial and caudal ends of the
digestive tract is derived from the ectoderm of the stomodeum and proctodeum
(fig. 11-1), respectively.
- The muscular and connective tissue components of the
digestive tract are derived from splanchnic mesenchyme surrounding
the primitive gut.
The FOREGUT gives rise to:
- the pharynx,
- the lower respiratory system,
- the esophagus,
- the duodenum (proximal to the opening of the bile duct),
- the liver,
- the pancreas,
- and the biliary apparatus.
Because, trachea and esophagus have a common origin, imcomplete
partitioning of the trachoesophageal septum results in stenoses or atresias,
with or without fistulas between them.
Development of the liver
The liver bud or hepatic diverticulum is
formed from an outgrowth of the endodermal epithelial lining of the foregut
(fig. 11-5). The epithelial
liver cords and primordia of the biliary system which develop from the hepatic
diverticulum, grow into the mesenchymal septum transversum (fig. 8-9). Between the layers of the ventral
mesentery, derived from the septum transversum, these primordial cells differentiate
into the parenchyma of the liver and the lining of the ducts of the biliary
- Hemopoiesis in the liver starts on week 6.
- Bile formation starts on week 12.
Development of the duodenum
Congenital duodenal atresia is due to the failure of vacuolization
and recanalization (week 8; fig. 11-6). This process occurs following the normal solid stage of the duodenum
(week 5). Obstruction of the duodenum can also be caused by an annular
pancreas (fig. 11-11), resulting
from parts of the pancreas developing around the duodenum.
Development of the pancreas
The pancreas is formed by dorsal and ventral
pancreatic buds (fig. 11-10)
originating from the endodermal lining of the foregut. When the duodenum
rotates to the right, the ventral pancreatic bud moves dorsally and fuses
with the dorsal pancreatic bud. The ventral pancreatic bud forms most of
the head of the pancreas and the dorsal pancreatic bud forms the rest. If
the duct systems from each pancreas fail to fuse, an accessory pancreatic
The MIDGUT gives rise to:
- the duodenum distal to the bile duct,
- the jejunum,
- the ileum,
- the cecum,
- the vermiform appendix,
- the ascending colon,
- and the right 1/2 to 2/3 of the transverse colon.
The midgut forms a U-shaped intestinal loop herniating
into the umbilical cord during week 6 because of the lack of room in the
abdomen : This is the physiological umbilical herniation (fig. 11-13, 11-14).
- While in the umbilical cord, the midgut loops rotates
90 degrees counterclockwise (fig.
- During week 10, the intestines return to the abdomen,
rotating a further 180 degrees (The Developing Human, 6th ed., p. 285,
fig. 11-13C-D). This is the reduction of the midgut hernia.
Omphalocele (fig. 11-17), malrotations and abnormalities of
fixation result from failure of return or abnormal rotation of the intestines
in the abdomen. Because the gut is normally occluded during weeks 5 and
6 due to rapid mitotic activity of its epithelium, stenosis, atresias and
duplications (fig. 11-24) may
result if the recanalization fails to occur or occur abnormally.
Various remnants of the yolk stalk may persist such as
Meckel's (ileal) diverticulum (fig. 11-21; fig. 11-22) which can become inflamed and
The Hindgut gives rise to:
- the left 1/3 to 1/2 of the transverse colon,
- the descending colon,
- the sigmoid colon ,
- the rectum,
- and the superior part of the anal canal.
The inferior part of the anal canal develops from the proctodeum
The caudal part of the hindgut (the cloaca; fig. 11-25) is divided by the urorectal septum
into the urogenital sinus and rectum. The urogenital sinus
gives rise to the urinary bladder and urethra. The rectum
and superior anal canal are separated from the outside by the anal membrane
which breaks down by the end of week 8.
- Anorectal malformations result from abnormal partitioning
of the cloaca by the urorectal septum into the rectum and anal canal posteriorly
and the urinary bladder and urethra anteriorly (fig. 11-29).
- Arrested growth and/or deviation of the urorectal septum
in a dorsal direction causes most of the anorectal abnormalities such as
rectal atresia and fistulas between the rectum and urethra, urinary bladder
Urogenital system embryology
The Developing Human - Clinically Oriented Embryology - Moore and Persaud, 8th
edition - Chapter 12
The urogenital system develops from:
- the intermediate mesoderm (fig. 12-1B),
- the mesodermal epithelium (mesothelium) of the peritoneal
- and the endoderm of the urogenital sinus (fig. 12-20A).
The intermediate mesoderm used to lie lateral to the somites,
then moved away from the somites during the lateral fold. It forms the urogenital
ridge (fig. 12-1F) which
is comprised of:
- a nephrogenic cord or ridge (fig. 12-2A)
- and a gonadal or genital ridge (fig. 12-29C).
3 successive sets of kidneys develop:
- The nonfunctional, rudimentary pronephroi develop
early in week 4. But they degenerate, leaving behind the pronephric ducts
which run to the cloaca (fig.
12-2). These ducts will remain for other kidneys.
- The mesonephroi develop later during week 4, serving
as temporary excretory organs.
- The functional metanephroi or permanent kidneys
develop early in week 5. They are functional by week 11-13 and excrete
urine into the amniotic fluid. This excretion continues during fetal life
and the fetus swallows this urine mixed in the amniotic fluid. It is then
absorbed in the stomach and duodenum to the blood for transport to the
placenta and disposal.
- If renal agenesis or urethral obstruction
occurs, oligohydramnios results.
- If esophageal or duodenal atresia occurs,
then polyhydramnios results.
The metanephros develops mesodermally from the metanephric
diverticulum or ureteric bud which is a dorsal outgrowth from
the mesonephric duct near the cloaca (fig. 12-6).
- Its stalk gives rise to the ureter (fig. 12-6C),
- its cranial end to the renal pelvis,
- its first 4 generations of tubules to the major calyces,
- its second 4 generations to the minor calyces (fig. 12-6D)
- and the remaining generations of tubules to the collecting
tubules (fig. 12-6E).
The metanephric diverticulum or ureteric bud
penetrates the metanephric mesoderm in the caudal part of the nephrogenic
cord and stimulates the formation of the metanephric mass or cap (fig.
The metanephric mesoderm gives rise to the nephrons
(glomerulus, Bowman's capsule, proximal convoluted tubule, loop of Henle
and distal convoluted tubule; fig.
12-7). The cortex of the kidney in the newborn contains mostly undifferentiated
mesenchyme; the nephrons continue to develop several months after birth.
Ascension of the kidneys (fig. 12-10): The kidneys are first
located in the pelvis ventral to the sacrum but gradually ascend to the
abdomen. They reach the adult position by week 9 having touched the suprarenal
glands (fig. 12-10). This
is due to the disproportionate growth between the lumbar and sacral regions:
the sacral region grows faster than the lumbar region.
The kidneys rotate 90 degrees from anterior to medial.
During their ascension, the blood supply changes continuously
so that an adult may have 2 to 4 renal arteries (fig. 12-11).
The suprarenal glands ( fig. 12-27):
- The cortex forms from the mesoderm,
- the medulla from neural crest cells (receiving preganglionic
sympathetic fibers from the celiac plexus).
The urinary bladder develops from the urogenital
sinus and the surrounding splanchnic mesenchyme (fig. 12-20). The urogenital sinus is comprised of 3
- The cranial or vesical region which will form
the bladder and which is attached to the allantois. After birth,
the allantois degenerates and becomes the urachus forming the median
umbilical ligament. The transitional epithelium of the bladder
develops from endoderm of the urogenital sinus.
- The middle or pelvic region.
- and the caudal or phallic region.
The female urethra and almost all of the male urethra
have the same origin.
The glans penis in the male develops from the ectodermal
glandular plate (figs. 12-24, 12-25)
Developmental abnormalities of
the kidney and excretory passages are common:
- Incomplete division of the metanephric diverticulum or
ureteric bud results in double ureter (fig. 12-12B-D) and supernumerary kidney (fig. 12-12F).
- Failure of the kidney to "ascend" from its
embryonic position in the pelvis results in an ectopic kidney that is abnormally
rotated (fig. 12-12B).
- Various congenital cystic conditions of the kidneys may
result from failure of nephrons derived from the metanephric mesoderm to
connect with collecting tubules derived from the metanephric diverticulum.
THE GENITAL OR REPRODUCTIVE SYSTEM
develops in close association with the urinary or excretory system.
Genetic sex is established at fertilization, but the gonads
do not begin to attain sexual characteristics until week 7. Early genital
development is referred to as the indifferent stage of sexual development:
the external genitalia do not acquire distinct masculine or feminine characteristics
until week 12.
Testes and ovaries are
derived from the mesodermal epithelium (mesothelium) lining the posterior
abdominal wall, the underlying mesenchyme and the primordial germ
The primordial germ cells form in the wall of the yolk
sac during week 4 (fig. 12-30).
They later migrate into the developing gonads at week 6 and differentiate
into the definitive germ cells (oogonia/spermatogonia).
The reproductive organs in both sexes develop from primordia
that are identical at first.
- Gonads develop at week 5 from thickened mesodermal epithelium
on the medial side of the mesonephros, at the gonadal ridge (fig. 12-29C).
- Primary epithelial sex cords
grow into the underlying mesenchyme (fig. 12-29).
- During this indifferent stage, an embryo has the potential
to develop into either a male or a female. The indifferent gonads
consist of a cortex and medulla.
- In the male (XY) the cortex regresses and the medulla
develops (fig. 12-31). The
reverse occurs in the female (XX).
At first both the male and the female have 2 pairs of genital
or sex ducts: the mesonephric (wolffian - medial) and paramesonephric
(müllerian - lateral) ducts (figs. 12-33 and 12-34).
Gonadal sex is determined by the Y chromosome, which exerts
a positive testis-determining action (TDF) on the indifferent gonad.
- In the presence of a Y chromosome, testes develop and produce an inducer substance stimulating
development of the mesonephric ducts into the male genital ducts (epididymis,
vas deferens and ejaculatory ducts; fig. 12-33A). Androgens from the fetal testes stimulate development
of the indifferent external genitalia into the penis and scrotum.
A suppressor substance (müllerian inhibiting substance), also
produced by the testes, inhibits development of the paramesonephric ducts.
- In the absence of a Y chromosome
and in the presence of 2 X chromosomes, ovaries develop,
the mesonephric ducts regress, the paramesonephric ducts develop (fig. 12-33B-C). The superior end
of these ducts open into the future peritoneal cavity. The lower end becomes
the uterus and uterine tubes
- The vagina develops from the vaginal plate
derived from the urogenital sinus, and the indifferent external genitalia
develop into the clitoris and labia (fig. 12-37D-H).
Persons with true hermaphroditism (ovo-testes - very rare) have
both ovarian and testicular tissue and variable internal and external genitalia.
Errors in sexual differentiation cause pseudohermaphroditism.
- Male pseudohermaphroditism results
from failure of the fetal testes to produce adequate amounts of masculinizing
hormones, or from production of the hormones after the tissue sensitivity
of the sexual structures has passed. Subjects are chromosomally male.
- Female pseudohermaphroditism
results from virilizing adrenal hyperplasia, a disorder of the fetal suprarenal
or adrenal glands that causes excessive production of androgens and masculinization
of the external genitalia. Subjects are chromosomally female.
Androgen insensitivity syndrome:
- Previously called testicular feminization syndrome.
The patient is a normal-appearing female with presence of
undescended testes and 46, XY chromosome constitution.The external
genitalia are female but the vagina ends in a blind pouch. The
uterus and uterine tubes are absent. uterine tubes are absent.
- Most abnormalities of the female genital tract result
from incomplete fusion of the paramesonephric ducts ( fig. 12-44).
- Cryptorchidism (undescended
testes; fig. 12-48) and ectopic
testes result from abnormalities of testicular descent (The gubernaculum
guides the processus vaginalis into the scrotum and the testes
follow; fig. 12-47).
- Congenital inguinal hernia
(fig. 12-49A-B) and hydrocele
(peritoneal fluid in the processus vaginalis and spermatic cord; fig.
12-49C-D) result from persistence
of the processus vaginalis (communication between the tunica vaginalis
and the peritoneal cavity).
- Failure of the urogenital folds to fuse normally in males
results in various types of hypospadias (opening of the external
urethral orifice on the ventral surface of the glans penis or on the ventral
surface of the body of the penis; fig. 12-42) or epispadia.
EMBRYOLOGY OF THE BRANCHIAL
ARCHES AND DERIVATIVES
The Developing Human - Clinically Oriented Embryology - Moore and Persaud, 8th
edition - Chapter 9
The branchial apparatus consists of (figs. 9-3, 9-4):
- Branchial or pharyngeal arches
- Pharyngeal pouches
- Branchial grooves
- Branchial membranes
Most congenital malformations of the head and neck originate
during transformation of the branchial apparatus into its adult derivatives.
The primitive mouth or stomodeum is separated from the
primitive pharynx by the buccopharyngeal (oropharyngeal) membrane (fig. 9-1E). This membrane ruptures
at about day 24 (fig. 9-1F),
bringing the primitive gut into contact with the amniotic fluid cavity.
Branchial arches develop early in week 4 as neural crest
cells migrate to the future head and neck region.
By the end of week 4, 4 pairs of branchial arches are visible,
the 5th and 6th being small. Branchial arches are separated by the branchial
grooves and are numbered in a craniocaudal sequence (fig. 9-3).
Initially, each pharyngeal arch consists of mesenchyme
derived from the intraembryonic mesoderm and is covered with ectoderm
externally and endoderm internally.
Neural crest cells migrate
into the arches, creating the swellings of the arches and contributing to
the arches, even though they are of ectodermal origin. Neural crest cells
give rise to specific skeletal structures.
The mesenchyme in the arches give rise to muscles.
A typical branchial arch contains (fig. 9-3C):
- an aortic arch
- a cartilaginous rod
- a nerve
- a muscular component
Derivatives of the branchial arch cartilages (fig. 9-5B)
1st branchial (mandibular) arch cartilage develops
- into malleus and incus (middle ear bones)
from its dorsal portion
- into the anterior ligament of the malleus and
the sphenomandibular ligament from the perichondrium of its intermediate
- into the primordium of the mandible from its ventral
2nd branchial (hyoid) arch cartilage develops:
- into the stapes (middle ear) and the styloid
process from its dorsal part
- into the stylohyoid ligament from the perichondrium
of its intermediate part
- into the lesser cornu and the superior part
of the hyoid bone from its ventral part
3rd branchial arch cartilage develops into the greater
cornu and inferior part of the body of the hyoid bone.
4th and 6th branchial arch cartilages fuse to form the
laryngeal cartilages, except for the epiglottis which forms
from the mesenchyme in the hypobranchial eminence (from the 3rd and 4th
Derivative of the branchial arch nerves (fig. 9-7):
- 1st branchial arch: Trigeminal (V) nerve (maxillary
and mandibular divisions only)
- 2nd branchial arch: Facial (VII) nerve
- 3rd branchial arch: Glossopharyngeal (IX) nerve
- 4th and 6th branchial arches: Vagus (X) nerve
Derivatives of the branchial arch muscles (fig. 9-6):
1st branchial arch:
- Muscles of mastication
- Mylohyoid and anterior belly of the digastric
- Tensor tympani
- Tensor veli palatini
2nd branchial arch
- Muscles of facial expression
- Posterior belly of the digastric
3rd branchial arch
4th and 6th branchial arches:
- Levator veli palatini
- Constrictors of the pharynx
- Intrinsic muscles of the larynx
- Striated muscles of the esophagus
PHARYNGEAL POUCHES (fig. 9-8) develop between the branchial
arches (1st pouch is found between the first and second branchial arches).
There are 4 pairs, the 5th is absent or very small.
The endoderm of the pharyngeal pouches and the ectoderm
of the branchial grooves contact each other to form the branchial membranes
separating the pharyngeal pouches and the branchial grooves.
Derivatives of the pharyngeal pouches (fig. 9-9)
1st pharyngeal pouch expands into a tubotympanic recess
- The expanded distal portion of the recess contacts the
1st branchial groove (this is the only branchial membrane to persist
in the adult) contributing to the formation of the tympanic membrane
- Only the 1st branchial
groove persists in the adult as the external acoustic meatus (fig. 9-8).
- The tubotympanic recess gives rise to the tympanic
cavity and the mastoid antrum. Connection between the tubotympanic
recess and the pharynx elongates to form the auditory tube.
2nd pharyngeal pouch contributes to the formation of the
palatine tonsil (fig. 9-8)
and the epithelial lining of the fauces.
3rd pharyngeal pouch contributes to the formation of the
inferior parathyroid glands (week 5- bulbar portion; fig. 9-8) and the thymus (elongate portion).
which migrate inferiorly (past the superior parathyroid glands of the 4th
4th pharyngeal pouch contributes to the formation of the
superior parathyroid gland (bulbar portion) and the parafollicular
cells or calcitonin cells of the thyroid gland (elongate portion - ultimobranchial
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