Embryology powerpoints

1. The cardiovascular system
2. The lymphatic system
SYSTEMIC EMBRYOLOGY
E M B R Y O L O G Y Mirosława Cichorek Ph.D. 2016/17
This material is only for MUG Students self-study.

Blood vessels formation by vasculogenesis
and angiogenesis
Vasculogenesis
the formation of new
blood vessels when
there are no
pre-existing ones
(vessels develop
de novo from mesoderm )
Angiogenesis
the formation of new
blood vessels from
pre-existing ones
proliferation of
endothetial cells

Places of hematopoiesis in embryonic
and fetal period.
1. YOLK SAC first two months
2. LIVER and SPLEEN 2-8 months
3. BONE MARROW from 5th month

D e v e l o p m e n t o f t h e h e a r t
Splanchnic lateral mesoderm
begining of 3rd week
heart tube
pericardial
cavity
heart primordium
Cardiogenic
area
Moore K.L. et al.: ”The Developing Human” (Elsevier Science, 2003)

Larsen W.J.: ”Human Embryology” (Churchill
Livingstone Inc., 1997)
Angioblastic
cords
18-19 days
Splanchnic lateral mesoderm
2 mm

18-19 days
20 days
22 days embryonic folding causes
fusion of two tubes into
Intraembryonic coelom forming
Mesodermal cells differentiate into:
endocardium, myocardium
2 endocardial heart
tubes
endocardium
myocardium
epicardium
pericardial cavity
angioblastic cords
2 endocardial heart tubes
single endocardial tube
pericardial cavity
gut
1 endocardial tube
Heart
wallContractions of heart muscles occur in
peristalsis-like waves from sinus venosus.
Moore K.L. et al.: ”The Developing Human” (Elsevier Science,
2003)

D e v e l o p m e n t o f t h e e n d o c a r d i a l t u b e
1. Endocardial tube
develops into 3 parts:
2. Endocardial tube
develops into 5 parts:
bulbus cordis
ventricle,
atrium,
bulbus cordis
ventricle
primordial atrium
truncus arteriosus
sinus venosus
ventricle
atrium
bulbus
cordis
sinus
venosus
truncus
arteriosus
24 days23 days S-shaped heart

3.
26 days
4.
28 days
S-shaped heart
V-shaped heart
atrium
atrium
Ventricle
(left ventricle)
bulboventricular loop
(right ventricle)
truncus arteriosus

Development of two atria and two ventricles
5 - 8 weeks
Partitioning of: atrioventricular canal,
primary atrium, primary ventricle,

Division of the atrioventricular canal into
left and rihgt canals by cushions

septum primum
(foramen secundum)
septum secundum
(foramen ovale)
Development of the right atrium and the left atrium
Larsen W.J.: ”Human Embryology” (Churchill
The interatrial septum is formed by two septa, the septum primum
and the septum secundum.
The septa both have large openings (foramen secundum, foramen ovale) that
allow the oxygenated blood entering from right to left atrium.

Muscular part of interventricular septum
Development of the right and left ventricles
Larsen W.J.: ”Human Embryology” (Churchill Livingstone Inc., 1997)
Median muscular ridge in the floor of the ventricle near its apex.

Muscular part of the interventricular septum
Interventricular
foramen

Membranous part
(7-8 weeks)
The interventricular septum is build of the muscular part ( )
and membranous part ( )

Development of a spiral aorticopulmonary septum
Two ridges grow from the opposite walls of the bulbus cordis and
truncus arteriosus (outflow tract).
Neural crest cells participate in the formation of the ridges.
atrium
ventricle
Ventral endocardial cushion
endocardium
myocardium
bulbar and
truncal ridges
dorsal endocardial cushion
Outflow tract

Growing ridges fuse and undergo a 180-degree spiraling.
Formed septum devides the outflow canal into
ascending aorta and pulmonary trunk.
Ridges
Right atrium
Right ventricule Left
ventricule
Endocardial cushions
Ascending
aorta
Pulmonary
trunk
8 weeksLarsen W.J.: ”Human Embryology” (Churchill Livingstone Inc., 1997)

epicardium develops after 4th week from
proepicardial organ (mesoderm of septum transversum)
atrium
ventricle
Ventral endocardial cushion
endocardium
myocardium
bulbar an truncal
ridges
Proepicardial organ

The cardiac conduction system (CCS)
(develops from 5th week)
1. the sinoatrial node (SA-node);
5th week in the right wall of the sinus venosus
2. the atrioventricular node (AV-node)
3. the His-Purkinje system
The CCS cells differentiate from a subset of cardiomyocytes.

From all organs heart gets
as the first
final anatomical structure
at 8th week.

Left horn at 10th week degenerates and gives oblique vein of left
atrium and coronary sinus.
Right horn will be a part of right atrium.
sinus venosus
vitelline vein
umbilical vein
heart
Sinus venosus development (4 - 10 weeks)
Sinus venosus - two horns: right and left; each horn enters three veins:
common cardinal, umbilical, vitelline
cardinal veins: anterior, common, posterior
Moore K.L. et al.: ”The Developing Human” (Elsevier Science,
2003)

D e v e l o p m e n t o f a r t e r i e s
Embryo 4 weeks (4 mm)
aortic arches dorsal aortes
intersegmental arteries
vitelline arteries
umbilical arteries

Aortic arches
4 -8 weeks aortic arches development
I arch part of maxillary arteries
II arch hyoid and stapedial arteries
III arch common and part of internal carotid
arteries
IV arch right: part of right subclavian artery
left: part of arch of aorta
VI arch right: distal degenerates
part of right pulmonary artery
(after birth ligamentum arteriosum)
left: part of left pulmonary artery
ductus arteriosus
(ductus Botalli)

Umbilical arteries: proximal parts - internal iliac arteries
superior vesical arteries
after birth distal parts - medial umbilical ligaments
Vitelline arteries - celiac artery to the forgut,
superior (midgut) and inferior (hindgut) mesenteric arteries.
Arteries differentiate up to 8th week.
Aortic sac – part of arch of aorta, branchiocephalic artery
(cords of umbilical arteries)

D e v e l o p m e n t o f v e i n s
Embryo 4 weeks (4mm)
sinus venosus
cardinal veins: anterior, common, posterior
vitelline veins
umbilical veins
HEART

Vitelline veins development
Vitelline veins – hepatic sinusoids, portal vein, mesenteric veins,
splenic vein, part of inferier vena cava, hepatic veins
liver
sinus venosus
cardinal veins
vitelline veins
umbilical veins
serce
vitteline vein
umbilical vein
inferior
vena cava
Hepatic
veins
Portal
vein
Splenic vein
Superior
mesenteric vein
duodenum
Sinus venosus
Vitelline
vein R Vitelline vein L.
disappears
hepatic
sinusoids
Moore K.L. et al.: ”The Developing Human”
(Elsevier Science, 2003)
Carlson B.M.: ”Human Embryology and Developmental Biology” (Mosby, Inc., 2004)
Inferior mesenteric vein

Umbilical veins development
liverumbilical
vein
sinus venosus
After birth left umbilical vein and
ductus venosus differentiate into:
ligamentum teres and ligamentum
venosum respectively.
5 - 8 weeks - right
umbilical vein degenerates
Blood from the placenta enters
fetus by left umbilical vein.
Ductus
venosus
8 - 12 weeks forms ductus
venosus by which oxygenated
blood from placenta enteres
inferior vena cava.
Inferior
vena cava
Umbilical vein
Carlson B.M.: ”Human Embryology and Developmental Biology” (Mosby,
Inc., 2004)

The final venous system arises from three systems of veins: cardinal
(anterior and posterior), subcardinal, supracardinal.
Over time, all three sets of cardinal veins in the body break up to varying
degrees.
Anterior cardinal veins:
• left degenerates
• left branchiocephalic vein from anastomosis between anterior
cardinal veins
• superior vena cava (SVC) from right anterior and common cardinal
veins
Posterior cardinal veins- root of the azygos vein, common iliac veins
Subcardinal veins – left renal vein, suprarenal veins, gonadal veins,
segment of inferior vena cava (IVC)
Supracardinal veins- azygos and hemiazygos veins, segment of IVC
inferior vena cava :
• hepatic segment from vitelline veins
• prerenal, renal , postrenal segments from supracardinal
and subcardinal veins

Arteries differentiate up to 8th week,
veins to 12th week

Oxygen saturation
Murphy P J Contin Educ Anaesth Crit Care Pain 2005;5:107-112

Cyanotic defects
Acyanotic defects
Atrial Septal Defects - patent foramen ovale
Ventricular Septal Defect
Aortic and Pulmonary stenosis
The tetralogy of Fallot
Patent ductus arteriosus
Problems to study

Lymphatic system
Thymus
Spleen
Tonsils
Lymphatic vessels and lymph nodes

4th week - endoderm of the 3rd
pouch proliferates, builds connective
tissue of the stroma - epithelial
reticulum
6th week - connective tissue which
comes from neural crest forms
capsules and septas; thymic lobes
8-10th week - prothymocytes from
fetal liver invade the thymus
12th week - cortex and medulla in
the thymic lobes form
14-15th week - Hassal’s corpuscles
secrete hormones; maturation of
cells starts
Maturation of T lymphocytes
The T lymphocytes leave the thymus
and populate other lymphoid organs
(lymph nodes, spleen)
as fully functional immune cells.
Thymus

falciform ligament
spleen
pancreas
liver
omental bursa
spleen
5 weeks mesoderm of dorsal
mesentery builds stroma and
capsule
S P L E E N
4 - 8 months place of
hematopoiesis
T and B lymphocytes enter
spleen forming the white
and red splenic pulp.
hepatogastric
ligament

T O N S I L S
Tubal (a pair), pharyngeal, lingual tonsils
THE PALATINE TONSILS
5th week - endoderm of 2 pharyngeal pouch proliferates and forms
epithelium and tonsillar crypts
• mesoderm - stroma of the palatine tonsil
• 20th week - lymphatic nodules are forming

5 weeks - mesodermal lymphatic capillaries and
lymph sacs (6) near veins.
1. Two jugular lymph sacs - near the internal
jugular veins
2. Two iliac lymph sacs - near the junction of the
iliac veins with posterior cardinal veins
3. One retroperitoneal lymph sac - in the
mesentery on the posterior abdominal wall
4. One cisterna chyli - dorsal to the
retroperitoneal lymph sac
Lymphatic vessels and lymph nodes
1
2
3 4
Inc., 2004)

8 weeks -
sacs develop into
lymph nodes and
lymphatic vessels
are forming.
Right and left thoracic ducts
Inc., 2004)

3 months - lymph nodes develop
• Mesoderm builds stroma
and capsule of the node.
• Lymphocytes T and B
migrate into lymph nodes at
the end of the fetal period
and after birth.
Right
lymphatic duct
Thoracic
duct
Cysterna
chyli
Inc., 2004)

Lymph nodes also develop in the
mucous membrane of the
respiratory and digestive
systems.

Gastrointestinal system
Respiratory system

Study the following chapters in books:
1.The developing human….. Moore P.
Chapters: 9,11,12
2.Human embryology and developmental biology. Carlson B.
Chapters: 15

PRIMARY GUT DEVELOPMENT
Yolk sac
3-4 weeks embryo folding
4. Oropharyngeal membrane
5. Cloacal membrane
1 2 3
4 5
1. foregut
2. midgut
3. hindgut
Primary gut:

Wall of the primary gut:
1. endoderm
(epithelium, glands)
2. splanchnic lateral mesoderm
(connective tissue, muscles)
Enteric ganglia of the gut in the:
• submucosa (Meisner’s plexus)
• muscles (Auerbach‘s plexus)
come from Neural Crest Cells

The various regions of the gut tract depends upon
a pattern set up by combinations of Hox genes.
Development of all parts of the gut depends on
endoderm and mesoderm interactions.
Morphological and histological differences of each
region concern mainly mucosa membrane and
muscles.
Main molecules involved in the digestive tract
differentiation are:
• Shh in the endoderm
• BMP-4 in the mesoderm

F O R E G U T
FOREGUT: pharyngeal apparatus
respiratory system
esophagus
stomach
part of duodenum
liver
pancreas
gallbladder and biliary ducts

The foregut differentiation
• the primordial pharynx and its
derivatives (oral cavity, pharynx, tongue,
tonsils, salivary glands)
• respiratory system
• esophagus
• stomach
• duodenum
• liver
• pancreas

• epithelium and glands - endoderm
• upper part - striated muscles -
IV-VI pharyngeal arches mesenchyme
• lower part - smooth muscles -
splanchnic lateral mesoderm
• 4th week - development begins
• 7th week - reaches its final relative length Its epithelium proliferates and
obliterates the lumen
• 8th week - recanalization
circular muscular layer (inner layer)
longitudinal muscular layer (outer layer)
• 12th week - glands
E s o p h a g u s

S t o m a c h )
4th week - fusiform enlargement
5th week- dorsal border grows faster - greater
curvature
6-7th weeks – rotation 90 degrees in
a clockwise direction around its longitudinal axis.
Glands differentiate in the late fetal period.

Mesenteries of the stomach.
The stomach is suspended by :
• ventral mesentary (the ventral mesogastrium)
• dorsal mesentery (the dorsal mesogastrium) which
after rotation forms omental bursa.
Omental bursa communicates with the peritoneal cavity
through the omental foramen.

D u o d e n u m
The caudal part of the foregut (celiac artery)
and cranial part of the midgut (superior
mesenteric artery).
• 4th week - C-shaped loop
epithelium proliferates, obliterates cavity of the
lumen
• 8th week - recanalization. At that time most
ventral mesentary of the duodenum dissapears

L i v e r
1. Hepatic diverticulum - 4th week, endoderm grows into
the mesoderm of septum transversum
Primordium of the liver (A) - liver
Biliary apparatus (B) - gallbladder
biliary duct system
A
B
HEPATOCYTES

2. mesoderm
septum
transversum
connective
tissue,
vessels
4th week
5th week
Because of liver growth ventral mesentery divides into:
lesser omentum (gastrohepatic omentum) and
falciform ligament.

During liver differentiation mesoderm and
endoderm influence each other - by a series of
inductive processes - but the exact mechanism is
unknown.

• from 6th week to 7th month fetal time
• Liver grows rapidly;
9-10 weeks, accounts 10% of the total weight of the fetus;
from 7th month 5%
• Main hepatocytes functions: 1. production of the main
protein of fetal serum
-fetoprotein
2. production of blood
coagulation proteins
3. glycogen synthesis (function
strongly stimulated by
adrenocortical hormones)
4. bile formation (12th week)
liver is a hematopoetic organ - blood cells formation

Pancreas development
5th week - buds of duodenum
dorsal bud (a)
ventral bud (b)
6th week - ventral bud
rotates with duodenum
and fuses with dorsal bud.
The exocrine part of
the pancreas consists of large
number of - acini with ducts
(endoderm). b
a
a
b b
duodenum
b
a
head tail
duodenum

Pancreatic (Langerhans) islets -
differentiate from ducts of acini at 12th week
 cells GLUCAGON
 cells INSULIN
 cells PP protein
 cells SOMATOSTATIN
secrete hormones from 20th week
Exocrine components - secrete digestive enzymes
Endocrine components - secrete insulin and glucagon

M I D G U T
MIDGUT: part of duodenum
small intestine (jejunum, ileum)
cecum and vermiform appendix
ascending colon
right part (2/3) of the transverse colon

• 6th week - the developing
intestines (the midgut loop)
projects into the umbilical
cord -
physiological umbilical
herniation
rotation 90 0 counterclockwise
• 10th week - intestines
return to the abdomen;
rotation 180 0
yolk stalk
5-8 weeks
rapid growth
6 weeks.
11 weeks
10 weeks
midgut
loop
Total rotation 270 0

4-6 weeks
allantois yolk stalk
cloaca
urorectal septum
cloacal membrane
urorectal septum growth
4th week
hindgut
Moore K.L. et al.: ”The
Developing Human” (Elsevier
Science, 2003)

7th week - urorectal septum divides the cloaca into:
- Urogenital sinus (ventrally)
- Rectum (dorsally)
urogenital membrane
anal membrane
8th week - anal membrane
ruptures
urogenital sinus
rectum
7 weeks
urorectal
septum

rectum canal:
urogenital sinus:
• 1/3 of the transverse colon
• descending colon
• sigmoid colon
• rectum
• urinary bladder
• urethra

Development of the digestive system
1.foregut:
2.midgut:
3.hindgut:
P
R
I
M
A
R
Y
G
U
T
pharyngeal apparatus (pharynx)
respiratory system
esophagus
stomach
part of duodenum
liver
pancreas
galdbladder
part of duodenum
small intestine (jejunum, ileum)
cecum and vermiform appendix
ascending colon
right part (2/3) of the transverse colon
1/3 of the transverse colon
descending colon
sigmoid colon
rectum
urinary bladder and urethra

INTRAEMBRYONIC COELOM
• Dorsal and ventral mesenteries seperate intraembryonic
coelom into right and left.
• Except region of the stomach and liver the ventral
mesentery disappears.
• The septum transversum divides the coelom into
thoracic and abdominal regions, which are connected by
pleural canals.
• The developing lungs grow into the pleural canals.

The definitive d i a p h r a g m is formed from:
the septum transversum
pleuroperitoneal folds
ingrowths from body wall
dorsal mesentery of esophagus
Esophagus
mesentery
Sadler T. W. „Langman’s Medical Embryology” , Lippincott Williams&Wilkins, 2010

Esophageal Atresia/Fistula /Stenosis
Duodenal stenosis/Atresia
Congenital omphalocele
Gastroschisis
Umbilical hernia
Annular pancreas / Accessory pancreatic tissue
Meckel's diverticulum
Congenital megacolon (HIRSCHSPRUNG'S DISEASE)
Problems to study:

Respiratory system
development

Development of the larynx:
pharyngeal arches IV and VI participate in
this structure development

Development of the respiratory system
FOREGUT - RESPIRATORY SYSTEM
4th week
endoderm: epithelium and glands
splanchnic: connective tissue,
mesoderm cartilages
muscles
blood and lymphatic
vessels

I. 4-7 weeks - embryonic
II. 8-16 weeks - pseudoglandular
III. 17-26 weeks - canalicular
IV. 26 weeks up to birth - terminal sacs
V. 32 weeks to 8 years - alveolar

4-7 weeks - laryngotracheal diverticulum -
ventral part of foregut;
tracheoesophagal septum - trachea and esophagus
main bronchi
lung buds grow into the pleural cavities.
Laryngotracheal
diverticulum
Bronchial
buds
Tracheoesophagal septum
Laryngotracheal
tube
Esophagus
Esophagus Lung bud
ENDODERM MESODERM

bronchial buds
3 bronchi
right lobe
2 bronchi
left lobe
Branching
– bronchial buds
– bronchi
three on the right and
two on the left

PSEUDOGLANDULAR STAGE
8-16 WEEKS
CANALICULAR STAGE
17-26 WEEKS

II. PSEUDOGLANDULAR STAGE 8 - 16 weeks
The respiratory tree of the lungs undergoes branching -
terminal bronchioles formation
(developing lungs resemble exocrine gland)
There are not elements envolved in the gas exchange.

The respiratory diverticulum
undergoes finally
23 sets of dichotomous
branching up to 24th week
Up to 16th week 16 generations
17-24 weeks 7 generations

In the epithelial cells adhesion molecules appear
e.g. integrins, cadherins.
Epithelial cells secrete:
VEGF (vascular epithelial growth factor) - stimulates blood
vessels formation in the mesenchyme

III. CANALICULAR PERIOD
17-26 weeks
Respiratory
epithelium
blood vessels development
stimulated by VEGF
secreted by epithelial cells
type I alveolar cells
(type I pneumocytes)
bronchi and terminal
bronchioles divide
dichotomically
respiratory bronchioles
24 weeks - terminal sacs begin to
develop (primordial alveoli).

In the epithelium of
forming alveoli are:
• type I pneumocytes
(gas exange)
Respiratory
epithelium
Capillaries
IV. TERMINAL SAC PERIOD
26 weeks to birth
With increasing amounts of surfactant
the fetus has a greater chance of
survive if born prematurely.
• type II alveolar cells
(type II pneumocytes;
secret surfactant)

Respiratory epithelium differentiates under influence of:
1. hormones - g l u c o c o r t i c o i d s
(secreted by adrenal glands) cells differentiation;
surfactant production increases
2. Growth factors secreted by mesenchyme cells:
e.g. EGF (amphiregulin)
FGF-7 (pneumocytes II differentiation)
TGF- (inhibits FGF-10 secretion)
3. Changes in the structure of the epithelial basal lamina

Capillaries are closed to respiratory epithelium.
Connective tissue reduction in the air-blood barrier.
Respiratory
epithelium
Capillaries
APOPTOSIS
of fibroblasts and mesenchyme cells

V. ALVEOLAR PERIOD
Late fetal period - 8 years;
about 85% of alveoli develop postnatally
The alveoli mature.

Terminal sacs
26 weeks
Alveoli
After 28 weeks fetus can breath if born prematurely.
In fetus lungs are filled with fluid.
During three days after birth lungs fill with air.
Newborn has 1/6 of alveoli, number increases up to 8th year.

Trachea endoderm - epithelium and glands
mesoderm - connective tissue, muscles,
cartilages

Problems to study
Laryngeal atresia
Tracheoesophagal fistula
Tracheal stenosis and atresia
Respiratory distress syndrome
Lung hypoplasia

The urogenital system
Molecular mechanisms of sex determination

Intermediate mesoderm at 4th week gives rise to
urogenital ridges
nephrogenic ridges
differentiation from 4th week:
- pronephros
- mesonephros
- metanephros (kidneys)
gonadal ridges
differentiation from 6th
week:
gonads: ovaries or testis

Nephrogenic ridge differentiation
Three sets of excretory organs develop in
human embryo:
pronephros, mesonephros, metanephros (kidneys)

Metanephros/permanent kidney
Intermediate mesoderm:
1. ureteric bud -
outgrowth from the mesonephric duct
near its entrance into the cloaca which
proliferates into direction of metanephric
mesoderm.
Ureteric bud is the primordium of the:
2. metanephric blastema
Collecting tubules induce metanephric
mesoderm (metanephric blastema) to
develop into elements of:
1 2
ureter, renal pelvis, renal calyx
and collecting tubule
nephrons
5 weeks
4-6 mm

5 weeks
6 weeks
16 weeks
Ureteric bud
Metanephric
blastema
Developing
nephron
lobes
Ureteric bud dichotomical divisions
Schoenwolf G. C. „Larsen’s Human Embryology” Churchill Livingstone, 2009

Renal pelvis
calyx
calyxes
Renal pelvis
Ureteric bud dichotomical divisions

Renal
calyxes
Renal pelvis
Ureter
Collecting
ducts
Metanephric
blastema

Collecting
duct
Induces
mesoderm
differentiation
into nephron
Mesoderm
vesicle glomerulus
8 weeks 10 weeks
Distal
convoluted
tubule
Henle’s
loop
Bowman’s
capsule
Renal corpuscule
Collecting
duct
Schoenwolf G. C. „Larsen’s
Human Embryology”
Churchill Livingstone, 2009
duct
NEPHRON
Proximal
convoluted
tubule

Nephrons formation
10 weeks
1. Distal
convoluted
tubule
2. Loop of
Henle
8 weeks
Collecting tubule
Metanephric vesicle
Metanephric tubule
Bowman’s capsule
(renal corpuscle)
Glomerules
3. Proximal
convoluted
tubule

Positional changes of the kidneys:
6 - 9 weeks kidneys migrate (ascend) and rotate medially 900.
During the 9th week kidneys come into contact with adrenal
glands.
Common
iliac artery
aorta

Kidneys begin filtration.
The fetal kidneys are subdivided
into lobes that are visible externally.
The lobulation usually disappears
during infancy as the nephrons grow.
15th week 20% of nephrons.

Urinary bladder
4-6 weeks
allantois yolk stalk
cloaca
urorectal septum
cloacal membrane
urorectal septum growth
4th week
hindgut

7th week - urorectal septum divides the cloaca into:
- urogenital sinus
- rectum
urogenital membrane
anal membrane
8th week - anal membrane
ruptures
urogenital sinus
rectum
7 weeks
urorectal
septum
Moore K.L. et al.:
”The Developing
Human”

urinary bladder
ureter
mesonephric
duct
urinary bladder
Urogenital sinus is
divided into three parts:
vesical (urinary bladder)
pelvic
phallic
(urethra,
prostate gland,
part of vagina)

Urinary bladder - endoderm - epithelium
mesoderm - muscles,
connective tissue
Allantois - urachus - median umbilical ligament

Chromosomal and genetical
sex determination

CHROMOSOMAL SEX DETERMINATION:
XX + 22 pairs autosomes = female, homogametic
XY+ 22 pairs autosomes = male, heterogametic

Chromosomal sex determination is established at
fertilization and depends upon whether
an X-bearing sperm or Y-bearing sperm fertilizes
the X-bearing ovum.
ovum (X + autosomes) + sperm (X + autosomes)
= female XX
ovum (X + autosomes) + sperm (Y + autosomes)
= male XY

Chromosome Y
• human Y chromosome contains about
80 genes
• in mammals, it contains the gene SRY,
which triggers testes development, thus
determining maleness

Chromosome X
• contains about 1100 genes
• carries hundreds of genes but few, if any, of these have
anything to do directly with sex determination;
- factor VII and IX from coagulation cascade proteins
- visual pigments in retina

1. color blindness sometimes called Daltonism
It is the inability to perceive differences between some
colors e.g. red and green type that other people can
distinguish
2. haemophilia A and B
factor VIII and IX deficiency
X-linked genetic disorders are more common in male.

Inactivation of one X chromosome in female.
Early in embryonic (about 16th day) development in females, one of
the two X chromosomes is inactivated in all somatic cells.
This phenomenon is called X-inactivation and creates a Barr body.
X-inactivation ensures that females, like males, have one functional
copy of the X chromosome in each body cell.
Trophoblast - father’s X chromosome is inactivated
(extraembryonic membranes: amnion, placenta,umbilical cord)
Genome imprinting.
Embryoblast - X-inactivation in the female embryo is random.
There is no predicting whether it will be the maternal X or the
paternal X that is inactivated in a given cell.

Inactivation mechanism
Inactivation of X chromosome requires a gene on that chromosome
called XIST.
 XIST encodes a large molecule of RNA
(there is no translation process)
 XIST RNA accumulates along the X chromosome
containing the active XIST gene and proceeds to
inactivate genes on that chromosome converting it into an
inactive Barr body.

Active X chromosome has
methylated XIST (inactive gene).
Genome imprinting.

Chromosome Y determines male phenotype (1959).
Short arm of Y chromosome has
a gene SRY
(sex determining region Y)
gene SRY plays as trancsription factor for genes responsible for testis
differentiation (testis determining factor)

Gonadal ridge cells differentiate into
Leydig cells which secrete
testosteron
Cells of medullary sex cords
differentiate into Sertoli cells
and secrete AMH/MIS
(anti-mullerian hormone, müllerian
inhibiting substance)
during fetal life induces
differentiation of male
genital duct system and
the brain
At puberty causes the seminiferous
tubules to canalize, mature, influence
spermatogenesis and other secondary
sexual characteristics
dihydrotestosteron
during fetal life causes
external genitalia
differentiation and the
prostate development
AMH induces degeneration of
the paramesonephric
(müllerian) duct
there is no uterine tubes, uteres
and vagina.
AMH is active at 8-9 weeks.
In genetic male as the result of SRYgene expression:

Genetic females - lack of SRY gene

XX
Wnt4
other genes e.g.Rspo1
ovary
XY
Sry
Sox9
other genes e.g. SF1
testis
Sry - chr.Y Sox9 - chr.17
SF1 - chr .9
Genes determinig gonads development

Abnormal number of sex chromosome
I. Lack of sex chromosome
X0 Turner syndrome (1:3000)
II. More sex chromosome
XXY Klinefelter’s syndrome (1:1000)
XXX (1:1000)
XYY (1:1000)

Sex determination
1. Gonads development
2. Genital ducts and external genitalia differentiation
3. Gametes production
Genotype determines gonads: testis (Sry), ovary (lack Sry)
Gonads produce hormones which influence genital ducts
and external genitalia differentiation.

1. chromosomal -
fertilization
2. genetic
3. hormonal
male
sperm with Y
XY - male
in Y chromosome
testis
testosterone
AMH
Sex determination:
female
sperm with X
XX - female
lack of SRY gene
ovary
estrogens
SRY gene

M A L E H O R M O N E S
1. TESTOSTERONE
The Leydig cells produce small amounts of testosterone
during the embryological period.
Testosterone plays role in the testis differentiation.
2. MIS (AMH)
Anti-Mullerian hormon produced by Sertoli cells causing
mullerian ducts degeneration in male fetus.
Male fetus does not produce sperm cells.

FEMALE HORMONES
1. ESTROGENS e.g. estradiol
During fetal period small amounts of this hormone are produced.

Gonads and genital ducts development
Male
testis
• ductus epidydimis
• ductus deferens
(spermatic duct)
• seminal vesicles
Female
ovary
• uterine
tubes
• uterus
• vagina
Mesonephric
ducts
Paramesonephric
ducts
Gonadal ridges

Gonads
Gonads:
ovaries, testes
from gonadal
ridges and
gonocytes

Up to 6 weeks gonads are morphologically undistinguishable -
indifferent stage
(genetical differentiation at fertilization: XY - testis; XX - ovary)
The morphologically indifferent gonad consists of three populations of
cells:
1. primary sex cords cells - mesothelial epithelium covering ridge grows
into cord of ridge to form primary sex cords
2. mesodermal cells of ridge
3. gonocytes - primordial germ cells migrate from the wall of yolk sac to
the gonads.
1
2
3
3

In genetic male SRY gene expression causes:
Gonadal ridge cells
differentiation into
Leydig cells
differentiation into
Sertoli cells
with gonocytes form
seminiferous tubules.
(7th week)

testis - seminiferous tubules,
gametes production
at puberty
ovary - primary follicles -
primary oocytes with follicular cells
in fetus

Testis differentiation
at 7th week under
influence of
gene SRY.
Sertoli cells follicular cells
spermatogonia oogonia
seminiferous tubules primary follicules
Leydig cells
1. Sex cords cells
2. Gonocytes
1+2=
3. Mesoderm of ridge
TESTIS OVARY
At 12th week
primary follicules
form.

gonadal ridge
gonadal ridge
mesonephric duct
gonocytes
paramesonephric
duct (6th week, invagination of
mesothelial epithelium)
Mesonephric ducts
• duct of epididymis
• deferens (spermatic) duct
• ejaculatory duct and
seminal vesicles
Paramesonephric ducts
• uterine tubes
• uterus
• upper part of vagina
Genital ducts

Gonadal ridge cells differentiate into
Leydig cells which secrete
testosteron
differentiate into Sertoli cells
and secrete anti-mullerian hormone
AMH (antimullerian hormone)
(MIS -müllerian inhibiting
substance)
during fetal life induces
differentiation of male
genital duct system and
the brain
At puberty causes the seminiferous
tubules to canalize, mature, influence
spermatogenesis and other secondary
sexual characteristics
dihydrotestosteron
during fetal life causes
external genitalia
differentiation and the
prostate development
AMH induces degeneration of
the paramesonephric
(müllerian) duct
there is no uterine tubes, uteres
and vagina.
AMH is active at 8-9 weeks.
In genetic male as the result of SRYgene expression:

Male and female embryos have mesonephric (Wolff) and
paramesonephric (Mullerian) ducts but development of these structures
depend on an embryo sex:
Male embryo
8-10 weeks - paramesonephric
ducts degenerate under influence of
MIS/AMH (hormone secreted by
Sertoli cells)
8-12 weeks - mesonephric ducts
under influence of testosterone
secreted by Leydig cells develop
into:
duct of epididymis
deferens duct
ejaculatory duct
Female embryo
Paramesonephric ducts
differentiate into:
uterine tubes
uterus
part of vagina

Development of the broad ligament
of uterus.
Gonads descending (gubernaculum)

Testes descend into the
scrotum
12 weeks fetus up to
3 month after birth

Uterus
Paramesonephric duct
Urogenital sinus

4-6 weeks
The external genitalia develop from
the same primordia in both sexes

From 14th week male fetus is
distinguishable in USG.

PSEUDOHERMAPHRODITISM
ANDROGEN INSENSITIVITY SYNDROME
HYPOSPADIAS
BICORNUATE UTERUS
CRYPTOCHIDISM
CONGENITAL INGUINAL HERNIA
PROBLEMS TO STUDY
HORSESHOE KIDNEY
ACCESSORY RENAL ARTERIES
RENAL AGENESIS
ECTOPIC KIDNEY
POLYCYSTIC KIDNEY DISEASE

Nervous system
Eye
Endocrinal glands part 2
(adrenal glands, pituitary gland, pineal gland)

Study the following chapters in books:
1.The developing human….. Moore P.
Chapters: 18,19,13(adrenal glands)
2.Human embryology and developmental biology. Carlson B.
Chapters: 11,12,13

Amnion
Neural fold
Neural plate
Neural groove
Somites
Primitive streak
18 days 20 days
23 days
anterior
neuropore
posterior
neuropore
22 days
1. Anterior
neuropore closed at
25-26 days
2. Posterior
neuropore closed at
27-28 days
Neural tube

Differentiation of neural tube in
anterior-posterior axis

Neural tube differentiation in
A-P axis
1. 2/3 neural plate - brain
- 3 later 5 vesicles
- flexures: midbrain, cervical,
pontine
2. 1/3 spinal cord
Neural tube is divided into:
prosomeres (forebrain)
rhombomeres (hindbrain)
Prosomeres 1-6
Rhombomeres 1-7
NEUROMERES

Cells in the cranial part of neural tube proliferate
and in 4th week 3 vesicles:
Brain development
1. Forebrain - prosencephalon
2. Midbrain - mesencephalon
3. Hindbrain - rhombencephalon
spinal cord
cervical flexure
midbrain flexure
hindbrain
rhombomeres
forebrain midbrain
optic
vesicle
Cochard L.R.: ”Netter’s Atlas of Human Embryology” (MediMedia, Inc., 2002)

From 6th week brain has 5 vesicles:
1. telencephalon - cerebral hemispheres
2 .diencephalon - thalamus and hypothalamus,
retina, posterior pituitary gland,
pineal gland
3. mesencephalon - somatic efferent nuclei
of cranial nerve III and IV supplying muscles of
eye;
- coordination of vision and hearing
- cerebral peduncles
4. metencephalon - pons and cerebellum
5. myelencephalon - medulla oblongata
telencephalon
diencephalon
midbrain
metencephalon
myelencephalon
Cochard L.R.: ”Netter’s Atlas of Human Embryology”
(MediMedia, Inc., 2002)

Ventricles, meninges,
cerebrospinal fluid (CSF)

The ventricles are lined by ependymal epithelium and
filled with cerebrospinal fluid (CSF).
CSF is formed in choroid plexuses.

Mesenchyme surrounding neural tube forms meninges:
dura mater
arachnoid mater
(subarachnoid space) CSF
pia mater

Differentiation of neural tube in
dorsal-ventral axis

Neural tube differentiation in D-V axis
Roof plateBMP
Floor
plate
1. Alar plate - dorsal
SENSORY - afferent
(interneurons)
2. Basal plate - ventral
MOTOR - efferent
(motoric neurons)
notochord
3. Sulcus limitans
Shh

Neurogenesis
Proliferation and differentiation of cells.

Cells in the neural tube
proliferate -
neuroepithelium

neuroepithelium
neuroblasts
glioblasts
ependym
ocytes
astrocytes
oligodendro
cytes
microglial cellsmesenchyme
neurons
Cell lineages in the nervous system

One of the fundamental process in the brain is cell
migration.
Neuroblasts migrate from ventricular zone toward the
periphery forming layers in the brain cortex and cerebral
cortex.
Cochard L.R.: ”Netter’s Atlas of Human Embryology” (MediMedia, Inc., 2002
Migrating neuroblasts
Neuroblasts migration
ventricular zone

Neuroblasts migrate on the
radial cells
The brain cortex has six
layers - the most inner
migrate first.
In the migration adhesion
molecules play significant
role
e.g. N-cadherin
Carlson B.M.: ”Human
Embryology and
Developmental Biology”
(Mosby, Inc., 2004)
radial
cell
neuro
blast
Ventricular
zone
Marginal
zone

65
days
100
days
6 months
final cortex
Histogenesis of brain cortex
1
2
4
3
5
6
1-2 months
-primitive
cortex
3-7 months
- neocortex
3-6 months -
cell proliferate
and migrate;
layers
formation
7 months -
neurons
specialization

Neurons loose ability to proliferation
during the fetal time.
Glial cells have ability to proliferation
during postnatal time.

When neurones take theirs
final position the outgrowth
of axons and dendrites
starts.
The outgrowth of axones and
dendrites
dendrites
axon
This growth is under
influence of many factors
e.g. NGF (nerve growth
factor) secreted by target
cells e.g. muscles.
Adhesion molecules e.g. N-,
E-cadherins are involved in
the process of neurites
movement.

Motoric neurones
Axons of
motoric neurones
Axones growth
into myotomes

When an axon and a target (muscle) meet
a synapse is formed
Synapses formation
Neurones which do not build synapses dye by
APOPTOSIS

Myelination of nervous fibres in
the central nervous system:
7th month fetus to two years
old child
oligodendrocytes (neural tube)
Myelination of nervous fibres in
the peripheral nervous system:
4th month fetus
lemmocytes (from NCC)
PNS CNS

Medullary cone
After 8 week 24 weeks newborn adult
Spinal ganglia
Root of
1st sacral nerve
Dura mater
S1
L3
L1
Changes in the level of the end of the spinal cord
Root of
1st sacral nerve
Medullary cone
Root of
1st sacral nerve

Brain weight after birth is 1/4 final weight,
up to the second year grows very fast
than slower up to 14th year.

Peripheral nervous system
• cranial nerves
• spinal cord nerves
• spinal ganglia
• ganglia of cranial V, VII, IX, X nerves
• autonomic ganglia: sympathetic and parasympathetic
NCC

sensory ganglion
autonomic ganglion
Unipolar neuron
Multipolar neuron
Cells of ganglia
NCC

Proteins which play main role in the regulation of
human development:
transcription factors – regulate genes expression
signaling proteins – influence on other cells
During development only 20% of all genes undergo
an expression, but with time different part of
genome are active.

3. others: family”hedgehog” e.g. Shh
Wnt family
Transcription factors:
1. homeodomene
2. zinc finger
Signaling proteins:
1. TGF-β family (transforming growth factor) about 30 proteins
e.g. TGF-β 1-5
BMP1-9 (bone morphogenetic proteins)
Nodal
2. FGF family (fibroblast growth factor) about 10 proteins
4. Notch

Shh (sonic hedgehog)
(1994)
One of the most important signaling protein in
development.
Secreted from the cell influence as the signaling molecule
genes expression of the target cell.
Secreted by notochord, primitive node,
floor plate in the nervous system.

Retinoic acid (RA) is the active form of
vitamin A and has many developmental functions
e.g. regulates expression of HOX genes,
influences neural tube and limbs differentiation
Examples of morphogens:
Shh, BMP (D-V neural tube differentiation)
retinoic acid (RA)
Morphogen a signaling molecule that acts directly on
cells produce specific cellular responses dependent
on morphogen concentration.
Morphogen gradients generate different cell types

1. Cornea
2. Iris
3. Ciliary body
4. Lens
5. Vitreous body
6. Retina
7. Choroid
8. Sclera
9. Anterior chamber
10. Posterior chamber
1
2
3
4
5
6
7
8
9
10

Eye develops from:
Spinal cord
cervical flexure
midbrain flexure
Optic
vesicle
hindbrain
rombomeres
forebrain midbrain
Neuroectoderm of forebrain
Surface ectoderm
Mesenchyme from NCC
Gene Pax-6 plays a prominent role in the eye development.

optic grooves
22 days
lens
placode
optic vesicle
22 days optic groove -
evagination of the
forebrain (diencephalon)
optic vesicle
5 weeks optic cup
inner layer- retina
outer layer- pigmented
epithelium of retina
inner layer
outer layer
R E T I N A
Optic stalk

Retina cells differentiation.
Inner layer - proliferation of cells
4/5 neural retina: 1. Rods and cones (photoreceptors)
2. Bipolar neurones
3. Ganglion cells - axons
form optic nerve
1/5 epithelium of iris and ciliary body
Retina differentiation 9 - 25 weeks
Outer layer developes into pigmented epithelium of retina

I R I S AND C I L I A R Y B O D Y
2. Ciliary body
a) epithelium - optic cup layers
b) stroma - connective tissue
muscles come from mesenchyme
( accomodation)
1. Iris
- epithelium - optic cup layers
- stroma - mesenchyme
- dilator of pupillae and
sphincter pupillae muscles
are from neuroectoderm of the
optic cup
(control diameter of the pupill)
- melanocytes
1
1
2
2
T.W.Sadler.Langman’s Medical Embryology Wolters Kluwer 2008
T.W.Sadler.Langman’s Medical Embryology Wolters Kluwer 2008

mesenchyme
surface ectoderm
lens placode
optic cup
optic stalk
lens vesicle
5 weeks
neuroectoderm
L E N S
1. Lens placode 4th week
(optic vesicle induces lens
formation)
2. Lens pit
3. Lens vesicle:
5 weeks - connection with
surface ectoderm is lost
lens vesicle

Anterior epithelium -
one layer cuboidal
epithelium (1)
Posterior epithelium -
lens fibers develop up to
20th year after birth (2)
7 weeks - cells from
posterior wall of lens
vesicle elongate in the
anterior epithelium
direction to form
primary l e n s f i b e r s
Lens vesicles differentiation into lens

C H O R O I D AND S C L E R A
mesenchyme
mesenchyme
7 weeks
15 weeks
5 weeks
The first choroidal blood vessels appear during 15th week;
by 22nd week arteries and veins are well visible.
Pupillary membrane – regresses 6-8th month

C O R N E A
2. mesenchyme 3. corneal
endothelium
2. membranes
and stroma
32
1. corneal
epithelium
11. surface ectoderm
10th week - begining of development
15 weeks
3. neural crest cells

Vitreous body forms in the cavity of the optic cup
mesenchyme cells secrete:
- colagen fibers
- glucosaminoglicans e.g. hyaluronic acid
Hyaloid artery - degenarates in vitreous body;
central artery of retina

Optic nerve
Axons of
ganglion cells
of retina;
8th week
1
1
1

extrinsic eye muscles - paraxial mesoderm of head
(somitomeres)
eyelids : 7 weeks - two folds of skin that
grow over the cornea
10 - 28 weeks adhere to one another
(conjunctival sac)
lacrimal glands – ectoderm, 6 weeks after birth tears
are produced

Development of the endocrinal glands
part 2
Pituitary gland (Hypophysis)
Suprarenal (Adrenal) glands
Pineal gland (Epiphysis)

PITUITARY GLAND:
1. anterior pituitary
(adenohypophysis) -
Rathke’s pouch - ectoderm
of stomodeal roof
2. posterior pituitary
(neurohypophysis) -
infundibulum -
neuroectoderm, floor of the
diencephalon
8th week - both ectodermal
primordia fuse
21st day
8th week
Hypophysis
Regressing stalk of
Rathke’s pouch
Rathke’s
pouch
infundibulum
6th week

From 8th week cytodifferentiation of cells
producing hormones:
STH (somatotropin;growth hormone),
ACTH (adrenocorticotropin)
then LH, FSH begins
Growth hormone is secreted from 10th week,
the rest from 12th week.

1. Pars anterior
(glandular part)
2. Pars intermedia 3. Pars nervosa
3
1
2
Pituitary gland
Neurosecretion from
hypothalamus:
•ADH 10-19 weeks
(antidiuretic hormone;
vasopressin)
•Oxytocin 10-12 weeks
adenohypophysis
neurohypophysis

5th week - cells from mesothelium (lateral mesoderm) proliferate,
migrate and form the fetal cortex - large acidophilic cells
8th week - migration of neural crest cells (NCC) to the medial side
of the fetal cortex to form medulla.
12th week - next wave of mesodermal cells surrounding the fetal
cortex differentiate into permanent cortex - lower basophilic
(alkaliphilic) cells

Permanent cortex in the fetal period secretes mainly
GLUCOCORTICOIDS (e.g. cortisol).
• In the fetus, the cortex of adrenal glands consists of 80% of these
glands mass
• At 5th month its weight is 4g and production of hormones is
200mg/day
• Fetal cortex regresses during the first year of child
(1g in one-year-old baby)
Hormones necessary to maturation of: lungs, liver
and epithelium of the digestive tract.
The fetal adrenal cortex produces a precursor for the steroid
hormones synthesis by the placenta.

PINEAL GLAND (EPIPHYSIS)
7th week - diverticulum of the caudal part of the roof of the
diencephalon
6th month - pinealoblasts and glial cells
MELATONIN - INHIBITION OF GONADOLIBERINE SECRETION
REGULATES CIRCADIAN RYTHMS
(up to 3rd year child’s epiphysis secretes a lot of melatonin - child sleeps
14hrs/twenty-four hours).

From 12th week hormones synthesis occurs in the
fetal endocrinal glands:
thyroid, adrenals, gonads, pancreatic islets.
Embryo 6-7 weeks - hormones are secreted by trophoblast.
Pituitary gland hormones stimulate secretion of
peripheral endocrine glands mentioned above.
The development of prenatal endocrine function
occurs in several phases.

Anencephaly
Meningoencephalocele
Spina bifida
Meningomyelocele and myelocele with spina bifida
Hydrocephalus
Holoprosencephaly
Arnold-Chari malformation
Congenital adrenal hyperplasia
Problems to study:

Ear development
Skeletal system
Muscular system
Integumentary system
HOX genes

external ear:auricle
external acoustic meatus
tympanic membrane
middle ear tympanic membrane
tympanic cavity
ear bones
auditory (Eustachian) tube
inner ear: cochlea (hearing organ)
vestibular apparatus (balance organ)

Inner ear development
2. Cochlea
6 -10 weeks
1. Vestibular apparatus
6 - 7 weeks
otic placode (surface
ectoderm)hindbrain
otic pit
otic vesicle
22 days
28 days

Otic vesicle differentiation
Membraneous labyrinth
(innervated by cranial nerve VIII:
vestibular branch, spiral branch)
Balance organ
6 - 7 weeks
Hearing organ
6 - 10 weeks

Differentiation of maculae and cristae 7 - 10 weeks
Elements of the balance organ:
- semicircular ducts - cristae ampullaris
- endolymphatic duct
- utricle
maculae
cristae maculae
- otoliths
Hair cells and supporting cells
Sensory structures in the vestibular apparatus:

Histogensis of the spiral organ of Corti
cytodifferentiation 3 - 5 months
inner and outer hair cells; supporting cells
Bony labirynth.
8 weeks

Malleus
incus
stapes
tympanic cavity and Eustachian tube - I pouch
ear ossicles: malleus, incus - I arch
stapes - II arch
5 month 9 month
6 weeks
Up to 8th month
surrounded by
mesenchyme

External ear
• external auditory meatus
first pharyngeal groove,
ectodermal cells proliferate to
form meatal plug which
degenarates up to 8th month,
final length 9 years after birth
• auricle
mesenchyme of I and II arch
• tympanic membrane
first pharyngeal membrane
I arch II arch
I groove6 weeks
Auricular hillocks (6)

The skeletal system develops from
mesenchyme originated from
mesoderm and neural crest cells.
2. Somites: Sclerotome - cranial basis of the skull
and vertebral column, ribs
3. Somatic lateral mesoderm - bones of limbs,
shoulder and pelvic girdles
sternum
4. Mesnchyme of the head face bones
(paraxial mesoderm, NCC)
1. Somitomeres + NCC - cranial vault of the skull

THE AXIAL SKELETON:
• SKULL
• VERTEBRAL COLUMN
• RIBS
• STERNUM

VISCEROCRANIUM
S K U L L
NEUROCRANIUM
CARTILAGINOUS N.
- cranial basis bones:
• occipital
• temporal
• sphenoid
• ethmoid
• nasal
• occipital somites
• bones formation
from 6th week
MEMBRANEOUS N.
calvaria, cranial vault
bones:
• frontal
• parietal
• squamous of occipital
• mesenchyme from
somitomeres and NCC
• bones formation
from 12th week

Flat bones of the cranial vault are separated
by dense connective tissue membranes that
forms the sutures.
Six large fibrous area - fontanelles - are
present where several sutures meet.

Fontanelles close:
posterior - 3rd month after birth
anterior - during 2nd year after birth

CARTILAGINOUS V.
middle ear bones:
malleus and incus (I arch)
stapes (II arch)
MEMBRANEOUS V.
• maxillary
• mandible
• zygomatic
• squamos temporal
• palatine
• nasal
• lacrimal
VISCEROCRANIUM
Mesenchyme of NCC origin
SKULL
NEUROCRANIUM

1. Small size of the jaws
2. Lack of teeth
3. Absence of paranasal sinuses
Viscecranium of a newborn is small compared with
neurocranium
Sutures permit the brain to enlarge during infancy and
childchood.
First 2 years - the period of most rapid postnatal growth
of the brain.
Calvaria encreases capacity until about 16 years.
Growth of face and jaws (eruption of primary and
permanent teeth).
Paranasal sinuses increase.

VERTEBRAL COLUMN
Stages in development:
Mesenchymal (4-week embryo)
Cartilaginous (6-week embryo)
Bony stage (ossification from 3rd month to 24 years after birth)

Vertebral column - at the end of 4th week cells from sclerotomes
differentiate into mesenchyme and migrate to:
1. around the notochord - body of a vertebra,
anulus fibrosus of intervertebral disc
2. surrounding the neural tube - arches and spinous processes
3. laterly to the body of vertebra - transverse process
ribs
somite
neural tube
dorsal aortas
notochord
migrating cells from sclerotome
body
anulus fibrosus
arch and process
Larsen W.J.: ”Human
Embryology” (Churchill

notochord
sclerotome
Sclerotome
Intersegmental
artery
nucleus
pulposus
artery
nerve
myotome
body
2
3
Each vertebra is formed by fusion of the posterior (caudal;
densly packed cells) half of one pair of sclerotome (2P) with
anterior (cranial; loosely packed cells) half of the subjacent
pair of sclerotome (3A).
Body of 1 vertebra comes from 2 pairs of sclerotomes.
disc
annulus
fibrosus

Hox genes
participate in
vertebras
differentiation.
6 weeks -
cartilaginous stage
Ossification from
3rd month to
24 years after birth.

• part from vertebral column side
comes from vertebra (paraxial mesoderm)
• part from sternum side is build by
lateral mesoderm
R I B S

• develops ventrolaterally in the body wall from
lateral mesoderm
• 6 weeks - 2 sternal bands
• 9 weeks - bands fuse craniocaudally
• centers of ossification appear before birth
9 weeks
6 weeks
newborn
STERNUM
Carlson B.M.: ”Human
Embryology and
Developmental
Biology” (Mosby, Inc.,
2004)

THE APPENDICULAR SKELETON:
• PECTORAL GIRDLES
• PELVIC GIRDLES
• LIMB BONES

pectoral girdle - first cartilages in 7th week
clavicle ossification from 8th week
pelvic girdle - first cartilages in 7th week
ossification 15 - 20 weeks.
All components of appendicular skeleton begin as cartilaginous
models from lateral mesoderm.

L I M B S
D E V E L O P M E N T

4-5 weeks - limb buds (upper
limb as the first) - elevations of
body wall build from
somatic lateral mesoderm
covered by surface ectoderm
At the apex of each limb the
ectodermal cells formed
29 dzień
apical ectodermal ridge - AER
Interactions between AER and mesodermal cells are essential
for limb developmemt.
AER induces proliferation and differentiation of mesodermal
cells into cartilages and connective tissue of limbs.

5weeks 6 weeks
7 weeks 8 weeks
6 weeks - hand and foot
plates with digital rays
7 weeks - rotation - on their
longitudinal axes in opposite
directions:
upper limb laterally 900
lower limb medially almost 900
6 - 8 weeks - myoblasts from
somites migrate to form muscles
Proximal cells in the forming limb
produce scatter factor: SF-1
stimulates myoblast migration
from somites.
Ossification from 12th week.8 weeks - separate digits

7 weeks - rotation - on their longitudinal
axes in opposite directions:
upper limb laterally 900
lower limb medially almost 900

7th week -
free digitals
apoptosis
BMP-4 expression in
tissue which degenerates

Molecules control limb bud development in three axes
AER

Limbs development is under control of:
HOX genes
growth factors e.g. FGF, TGF-, BMP
BMP concentration in the interdigital
mesoderm specifies the identity of the
digits.
The sequence of formation of the digits
is from fifth to first.
Early forelimb buds are characterized
by the expression of transcription factor
Tbx-5, whereas hindlimb buds express
Tbx-4.
Carlson B.M.: ”Human Embryology and
Developmental Biology” (Mosby, Inc.,
2004)

BONE AGE
Radiologists use the appearance of various
ossification centers to determine whether child has
reach his /her proper maturation age.
Useful information about bone age is obtained from
osssification studies in the hands and wrists of
children.

The skeleton of the limb arises from
lateral mesoderm.
Limb muscles arise from cells derived
from myotomes of somites
(paraxial mesoderm).

Skeletal muscle cells -
Smooth muscle cells -
surrounding digestive and
respiratory tract
Cardiac muscle cells -
surrounding heart tube
Muscles of face and head -
myotomes of somites
muscles of axial skeleton,
body wall and limbs
splanchnic mesoderm
splanchnic mesoderm
mesenchyme of head
(somitomeres, NCC)

mesodermal cells differentiate
into myoblasts and migrate to
target places
myotome
somite

At about 5th week trunk muscles develop from:
1. - extensor muscles of the neck and
vertebral column
2. - muscles of: limbs, abdomen, thorax,
diaphragm, tongue, intercostal
Epimere
Hypomere
MYOTOME
Epimere
(epaxial muscles)
Hypomere
(hypaxial muscles)

mononuclear multinucleated
Muscle
fibers
M Y O G E N E S I S
Sarcomeres

DEVELOPMENT OF THE SKIN
AND ITS DERIVATIVES

2nd month - ectoderm
proliferation; two layers
formation: basal
germinative layer,
periderm
3rd month - proliferation
and differentiation of
epidermis cells - migration
of melanoblasts and
Langerhans cells
3-4 month - papillary layer
of dermis;
epidermal ridges - pattern
is genetically determined
20 weeks - periderm
shedding
6 months - definitive layers
in epidermis
HAIR BULB
Epidermis
(ectoderm)
Dermis
(dermatome,
somatic
lateral
mesoderm)
4 5 12 14 16 20 23-28 WEEKS
MELANO-
BLASTS

During skin development ectoderm and
mesoderm inductive mechanisms are involved.
Fetal skin is covered by vernix caseosa -
protects skin from amniotic fluid.

HAIR from 9th week, but on the surface of the skin:
16th week - eyebrows
20th week - other places
lanugo
NAILS - 10 - 32 weeks - hands
10 - 36 weeks - legs
SEBACEOUS GLANDS - 12th week (produce sebum)
SWEAT GLANDS - 20th week
MAMMARY GLANDS
6 weeks - mammary ridges (milk lines)
15-20 weeks - lactiferous ducts formation
DERIVATIVES OF THE SKIN:

H O M E O B O X
(HOX)
G E N E S

H o m e o b o x (HOX) g e n e s
Well known role in development of
Drosophila melanogaster (fruit fly)
1. Maternal-effect genes (anterior-posterior
organization of body)
2. Segmentation genes
3. Homeotic genes - determine regional characteristic
(segment bearing antennae, wings, legs)

Homeotic genes determine the position of cells in each
segment of the body

- homeobox 180 nucleotides
Protein of 60 aminoacids
transcription factor
Homeotic gene
homeodomain
• Highly conserved genes
• Crucial to development
• Functions still not well understood

Hox A chromosome 7
Hox B chromosome 17
Hox C chromosome 12
Hox D chromosome 2
In human 39 HOX are divided into families: :
Human HOX genes
participate in the differentiation of :
- central nervous system
- vertebral column
- limbs
Retinoic acid affects A-P axis formation and HOX gene expression.
Genes are expressed in sequences that correlate with development
of specific regions.

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