Embryo Formation
gastrulation in the second week
three-layered flat structure develops from ICM
primary germ layers form
ectoderm
mesoderm
endoderm
cells in each layer begin to form specific organs controlled by homeotic gene expression
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Supportive structures from trophoblast
support and protect the embryo
earlier
chorionic villi
yolk sac
allantois
later
umbilical cord
amniotic sac
placenta
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The Primordial Embryo
germ layers develop into specific groups of structures
ectoderm
mesoderm
endoderm
Mistakes result in multiple births
dizygotic twins (fraternal)
two sperm fertilize two oocytes
same genetic relationship as any two siblings
monozygotic twins (identical)
both from a single fertilized ovum
identical genetically as clones
can be exposed to slightly different or same uterine environments
conjoined twins (MZ or DZ)
incomplete separation or fusion
of twins in uterine environment
Types of identical twins
Embryonic development
organogenesis
simple germ layers develop into distinct organs
organogenesis is complete by eighth week of gestation
Embryonic development
primitive streak develops into neural crest
stem cells along the back of the embryo
neural tube, notochord, heart, CNS, limbs, face, etc.
haploinsufficiencies of neural crest cells lead to defects
Treacher Collins syndrome is an autosomal dominant disorder of cranial neural crest cell development
Fetal growth after organogenesis
growth and maturation of organs
normal body proportions
bone replaces softer cartilage
nerve and muscle functions become coordinated
sex organs become more distinct by week 6
by week 12:
sucks thumb
kicks
makes fists and faces
beginnings of teeth
fetal movement may be
noticed by mother, monitored
Birth defects are possible
development takes 40 weeks
critical period of development in early weeks
genetic abnormalities, toxic substances, viruses
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teratogens are environmental agents that cause birth defects
Teratogens can cause birth defects
exposure to chemical or other agents
may depend on mother’s genotype
known teratogens include
thalidomide
cigarettes and alcohol
nutrients or vitamin deficiency
occupational hazards
viral infections
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fetal alcohol syndrome
phocomelia due to thalidomide exposure
amniotic bands due to constriction of amnion
spina bifida due to low levels of folic acid
Parent-of-origin effects due to methylation
parental origin influences phenotype
age of onset or symptom severity
mechanisms of parent-of-origin effects
differential genomic imprinting
can alter expression of gene
Genomic Imprinting
normal imprinting in genome
methylated DNA imprints
erased during meiosis
remethylated according to type of gamete
some genes normally methylated in females, some in males
Imprinting errors cause disease
imprinted region of chromosome 15
gene PWS methylated in eggs
gene AS (UBE3A) inactive in sperm
expression of a few genes surrounding PWS-IC
expression of large region at PWS-IC
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Imprinting errors cause disease
deletion of chromosome 15 imprinted region
Prader-Willi syndrome if deletion inherited from father (no active copy)
Angelman syndrome if deletion inherited from mother (no active copy)
Prader-Willi s. phenotype of obesity, NIDDM, excessive hunger, moodiness and conduct disorder
Angelman s. phenotype of failure to thrive, hyperactivity, muscle hypotonia, happy mood
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Importance of genomic imprinting
regulate abundance of key proteins in embryo
imprinted genes in clusters, controlled by imprinting centers
one gene in cluster could be essential
others imprinted in bystander effect
uniparental disomy
results in teratoma
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Changes in gene expression in development
over time, in different cell types
programmed differentiation of stem cells
cell, tissue, or organ/gland level
changes in sets of proteins available
everything in a cell is due to a gene product
inherited or acquired changes in gene expression: epigenetics
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Changes in gene expression in development
epigenetic changes
chromatin-based gene activation/silencing
changes to chemical groups associated with DNA
promote or restrict access of transcription machinery
changes replicated during synthesis phase
transmitted to daughter cells after cell division
nucleosomes pick up chemical modifications that enhance or resist condensation
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Changes in gene expression in development
hemoglobin switching in development
adult hemoglobin is a tetramer of
2 alpha chains (chm 11) and 2 beta chains (chm 16)
adult hemoglobin has a high cooperative affinity for oxygen
fetal hemoglobin has an even higher cooperative affinity for oxygen
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Developmental hemoglobin chain switching
gene switching responds to oxygen levels
embryonic – 2 epsilon (e) + 2 zeta (z)
fetal – 2 gamma (g) + 2 alpha (a)
adult – 2 beta (b) + 2 alpha (a)
about 99% of hemoglobin molecules by four years of age
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Changing gene expression in environment
teratogen exposure
e.g., folic acid supplementation
donates methyl groups for DNA methylation
Does excessive folic acid lead to overmethylation of genes?
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Our Proteomes Change Over Time
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