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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 circulation12 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
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
10주7주
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
FE
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
(마더세이프라운드)  Embryogenesis - 제일병원 전이경 선생

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(마더세이프라운드) Embryogenesis - 제일병원 전이경 선생

  • 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 twos • Inner cell mass (embryoblast) – Epiblast – Hypoblast • Trophoblast – Cytotrophoblast – Syncytiotrophoblast • Extraembryonic mesoderm – Somatopleuric mesoderm – Splanchnopleuric mesoderm • Two cavities – Amniotic cavity – Yolk sac • Uteroplacental circulation12 days Amniotic cavity
  • 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
  • 9.
  • 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 4주말까지 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 defects • Most common CNS malformation, 1/1000 births • Primary non-close of the neural tube • Spectrum – Anencephaly – Meningocele – Meningoencephalocele – Meningomyelocele
  • 21. 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
  • 22. Holoprosencephaly 4th week, 4mm, 3 vesicle stage 5th week, 8 mm, 5 vesicle stage
  • 23. 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
  • 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 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 development
  • 31. Nasal pit Lateral nasal prominence Medial nasal prominence 5주 10주7주 6주
  • 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
  • 33.
  • 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
  • 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