1. The document discusses critical periods of human embryonic development from the first through eighth weeks. During this time, organ systems develop from the three germ layers and major malformations can occur if development is disrupted. 2. Specific processes discussed include gastrulation, neurulation, heart development and septation, palate formation, and limb bud emergence. 3. Teratogens acting during critical periods can cause defects such as neural tube defects, holoprosencephaly, cardiac defects, and limb abnormalities. Disorders from disrupted development of neural crest cells are also examined.

1. Human EmbryologyHuman Embryology
제일병원 병리과 전이경

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

3. First week of development:
ovulation to implantation
blastocyst
morule

4. 4.5
days
6
days

5. Second week of development:
bilaminar germ disc
Week of twosWeek of twos
• Inner cell mass
(embryoblast)
– Epiblast
– Hypoblast
• Trophoblast
– Cytotrophoblast
– Syncytiotrophoblast
• Extraembryonic
mesoderm
– Somatopleuric mesoderm
– Splanchnopleuric
mesoderm
• Two cavities
– Amniotic cavity12 days
Amniotic
cavity

6. Day 13

7. 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

8. Epiblast ->
1.ectoderm
2.mesoderm
3.endoderm
18-day embryo
1.25 mm in length

10. 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

11. 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

12. 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

13. Fate of the primitive streak
• intraembryonic mesoderm 을
4 주말까지 만들다가 감소
• insignificant structures in the
sacrococcygeal region of the
embryo
• Sacrococcygeal teratoma

14. 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.

15. 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

16. Formation of the notochord
B C

17. 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

18. 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

19. Final closure
Anterior neuropore: 25th
day
Posterior neuropore: 27th
day

20. Neural tube defectsNeural tube defects
• Most common CNS malformation,
1/1000 births
• Primary non-close of the neural tube
• Spectrum
– Anencephaly
– Meningocele
– Meningoencephalocele
– Meningomyelocele

21. AnencephalyAnencephaly
• 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

22. HoloprosencephalyHoloprosencephaly
4th
week, 4mm, 3 vesicle stage 5th
week, 8 mm, 5 vesicle stage

23. LissencephalyLissencephaly
• “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

24. Formation and migration of neural crest cells in the spinal cord

25. 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 derivativesNeural 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

26. Neural crest cells in conotruncal
region

27. 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).

28. 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

29. 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

30. 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

31. Nasal pit
Lateral
nasal
prominence
Medial
nasal
prominence
5 주
10 주7 주
6 주

32. 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
FE

34. A, day 18
B, day 20
C, day 21
D, day 22*
Heart tube

35. Atrial Septation (4-6 weeks)
Septum primum
ostium primum
Interventricular
foramen

36. ostium
secundum
Septum
secundum
35 days

37. Development of conotruncal ridges and
closure of the interventricular foramen
6 weeks Beginning of 7 weeks

38. End of 7 weeks

39. 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