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.
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
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
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
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
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
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
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
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
Notas do Editor
다양한 장기의 기형의 critical period에 대해 그려놓은 유명한 그림이지요. 제 가 오늘 강의에서 말씀드리는 날짜는 선생님들이 씃ㅣ는 날짜와 2주 차이가 있습니다. 저는 배란부터 시간을 세므로 제가 2주라면 선생님들은 2주를 더해서 4주로 생각하시면 됩니다. 수정되고 8주까지를 embryonic period 라 하고 세포 한 개에서 사람이 만들어 지는 정말 dynamic한 시기입니다. 이후에는 크기가 주로 커지는 fetal pe제riod 이구요. 3주에서 9주 초 까지 major morphologic abnormality가 생기는 시기이고 3주에 CNS anomaly를 선두로 heart anomaly 등 줄줄이 생기게 되는 데요. 제가 준비한 내용은 크게 두 부분이구요. 앞부분에서는 간단히 수정에서 neurulation시기까지 살펴보고 뒤는 심장발생을 좀 자세히 다루는 것으로 마무리 하겠습니다.
줄기세포의 특징
반복적으로 분열하면서 스스로 재생산 (unlimited self-renewal)
정상적인 다른 특정한 기능을 가진 세포로 분화(highly regulated differentiation)
배아줄기세포는 inner cell mass를 이용
발달과정과 같이 모든 신체기관으로 분화가 가능하기 때문에 다능성 줄기세포(pluripotent stem cell)라 부름