Human Embryology

제일병원 병리과 전이경

Critical periods of development for various organ systems and the resultant malformations

First week of development: ovulation to implantation

blastocyst

morule

4.5 days 6 days

Second week of development: bilaminar germ disc

Week of twos • Inner cell mass (embryoblast)

– Epiblast – Hypoblast

• Trophoblast – Cytotrophoblast – Syncytiotrophoblast

• Extraembryonic mesoderm – Somatopleuric mesoderm – Splanchnopleuric mesoderm

• Two cavities – Amniotic cavity – Yolk sac

• Uteroplacental circulation 12 days

Amniotic

cavity

Day 13

Third week of development: Trilaminar germ disc

Gastrulation

• Bilamelar germ disc is converted into a trilamelar germ – Ectoderm

– Mesoderm

– Endoderm

• Primitive streak – Thickened linear band of

epiblast

– 15- to 16-day embryo: clearly visible

Epiblast ->

1. ectoderm

2. mesoderm

3. endoderm

18-day embryo

1.25 mm in length

Derivatives of the ectodermal germ layer

1. Central nervous system

2. Peripheral nervous system

3. Skin, including hair and nails

4. Sensory epithelium of ear, nose, and eye

5. Pituitary, mammary, and sweat glands and enamel of the teeth

Derivatives of the mesodermal germ layer

• Connective tissue, cartilage, bone and striated and smooth muscles

• heart, blood and lymph vessels and cells

• kidney, ovary and testis, genital ducts, serous membranes lining, spleen, and adrenal cortex

Derivatives of the endodermal germ layer

1. Epithelial lining of the gastrointestinal tract, respiratory tract, and urinary bladder

2. Parenchyma of the thyroid, parathyroid, liver and pancreas

3. Epithelial lining of the tympanic cavity and auditory tube

Fate of the primitive streak

• intraembryonic mesoderm 을 4주말까지 만들다가 감소

• insignificant structures in the sacrococcygeal region of the embryo

• Sacrococcygeal teratoma

Teratogenesis associated with gastrulation

• The beginning of the third week of development, when gastrulation is initiated, is a highly sensitive stage for teratogenic insult.

• At this time, fate maps can be made for various organ systems, such as the eyes and brain anlage, and these cell populations may be damaged by teratogens.

• For example, high doses of alcohol at this stage kill cells in the anterior midline of the germ disc, producing a deficiency of the midline in craniofacial structures and resulting in holoprosencephaly.

Caudal dysgenesis (sirenomelia)

• Insufficient mesoderm in the lumbosacral region of the embryo

− Hypoplasia and fusion of lower limb

− Vertebral abnormalities

− Renal agenesis

− Imperforate anus

− Anomalies of the genital organs

Formation of the notochord

B C

Notochord: 1. Primitive axis of the embryo

2. Induction - neural plate (future nervous system)

Fate of the Notochord:

– Regress in the vertebral bodies

– Intervertebral disc: persist as the nucleus pulposus

20 days

Neurulation includes

the formation of the neural

plate (day 18-19), neural

folds (day 20-21), and the

neural tube (day 22-26); the

latter will develop into the

future brain and spinal

cord

Final closure

Anterior neuropore: 25th day

Posterior neuropore: 27th day

Neural tube defects

• Most common CNS malformation, 1/1000 births

• Primary non-close of the neural tube

• Spectrum – Anencephaly

– Meningocele

– Meningoencephalocele

– Meningomyelocele

Anencephaly • Absence of scalp, calvarium,

and normal brain -> “frog’s face”

• Area cerebrovasculosa

• Hypoplastic adrenal glands with absent fetal zone

• Recurrence rate: 3-5%

• DDx: amniotic disruption sequence

Amnion

disruption

consequence

Anencephaly

Holoprosencephaly

4th week, 4mm, 3 vesicle stage 5th week, 8 mm, 5 vesicle stage

Lissencephaly

• “Smooth brain”

• Severity : the absence (agyria) to reduction (pachygyria) of normal gyral pattern.

• Classic L./cobblestone L.

• Onset : no later than the 12th–16th week of gestation

• DDx: immature GA (until 27-28W)

•GA 31 wks

•46, XX, del(17)(p13)

•“Miller-Dieker” syndrome

Formation and migration of neural crest cells in the spinal cord

Neural crest cells • Vulnerable cell population

• Easily killed by compounds such as alcohol and retinoic acid.

• Deficient in superoxide dismutase and catalase enzymes that are responsible for scavenging free radicals.

• Neural crest derivatives Connective tissue and bones of the face and skull Dermis in face and neck

☞ Severe craniofacial malformations ☞ Treacher-Collins' Syndrome, DiGeorge anomaly...

Conotruncal septum in the heart ☞ cardiac anomalies including persistent truncus arteriosus,

TOF and TGA Cranial nerve ganglia, spinal ganglia, sympathetic chain and

preaortic ganglia, parasympathetic ganglia of the gastrointestinal tract, glial cells, schwann cells, adrenal medulla, C cells of the thyroid gland, arachnoid and pia mater, melanocytes, odontoblasts

Neural crest cells in conotruncal region

MIGRATION PATHWAYS OF

NEURAL CREST CELLS

from forebrain, midbrain,

and hindbrain regions into

their final locations (shaded

areas) in the pharyngeal

arches and face

Skeletal structures of the

head and face. Mesenchyme

for these structures is

derived from neural crest

(blue), lateral plate

mesoderm (yellow), and

paraxial mesoderm (red).

Treacher-Collins' Syndrome /

mandibulofacial dysostosis

• Characterized by malar hypoplasia due to underdevelopment of cheek bones, mandibular hypoplasia, down-slanting eyes and malformed external ears

• Normal development and intelligence

• AD with variable penetrance

• 60% as new mutation

www.treachercollins.org/main.ht

ml

Velocardiofacial Syndrome/DiGeorge anomaly

• 22q11.2 deletion

• “CATCH 22”

– Cardiac defects

– Abnormal face

– Thymic hypoplasia

– Cleft palate

– Hypocalcemia

• Abnormal development of neural crest cells

• Specific facial features – low-set ears, wide-set eyes,

a small jaw, and a short groove in the upper lip

• Etiology – Genetic causes, exposure to

retinoic acids, alcohol, and maternal DM

Limb growth and development

A. 5-week embryo B. 6-week embryo C. 8-week embryo

The hindlimb buds are less well developed than those of the forelimbs.

The most sensitive period for teratogen-induced limb malformations is the fourth and fifth weeks of development

Nasal pit

Lateral nasal prominence

Medial nasal prominence

5주

10주 7주

6주

A.B. 6.5-week embryo

The palatine shelves

are in the vertical

position on each side

of the tongue.

C.D. 7.5-week embryo

The tongue has

moved downward,

and the palatine

shelves have reached

a horizontal position.

E.F. 10-week embryo

The two palatine

shelves have fused

with each other and

with the nasal septum.

C D

F E

A, day 18

B, day 20

C, day 21

D, day 22*

Heart tube

Atrial Septation (4-6 weeks)

Septum primum

ostium primum

Interventricular

foramen

ostium

secundum

Septum

secundum

35 days

Development of conotruncal ridges and closure of the interventricular foramen

6 weeks Beginning of 7 weeks

End of 7 weeks

Third to eighth week: The embryonic period

• Period of organogenesis

• Each of three germ layers gives rise to its own tissues and organs.

• Major features of the external body form recognizable by the end of the second month