The early development of Mammals

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The early development of Mammals

• Mouse
• Human

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• Why the mouse?
• Advantages
• Short life cycle-9 weeks
• Amenable to genetic analysis and mutation
• Similar developmental pattern to human
• Disadvantages
• 1. Development happens inside the mother.

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The unique nature of mammalian cleavage

• Slowness of cleavage
• Unique orientation----rotational cleavage
• Asynchrony of early cleavage----odd number
  blastomeres
• Early activation of zygotic gene transcription
  ---2 cell stage
• Compaction

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• Cleavage
• Starts 24 hr after fertilization and 12 hr /cut
• Happens in the oviduct
• Rotational cleavage
• Compaction creates solid ball of cells called
  morula
• After compaction, blastomeres are polarized.

cleavage
Cleavage 24 hr4.5 day Blastocyst 3.5 day Hatch
out 4.5 day Implantation 4.5 day Gastrulation
4.5 10 Organogenesis 10-19 day Birth 19 day
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Summary of the Main Patterns of Cleavage
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Early Cleavage in (a) Echinoderms and Amphibians
and (B) Mammals
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The Cleavage of a Single Mouse Embryo In Vitro
Cavitation the blastocoel is created by the
trophblasts pumping Na into the central cavity
and followed by inflow of water.
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SEMs of (A) Uncompacted and (B) Compacted 8-cell
Mouse Embryos

• E-cadherin expressed
• Cell huddled together
• Stabilized by tight junction
• Gap junction form between blastomeres

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Compaction At 8 cell stage, blastomeres increase
the area of cell surface in contact with each
other and results in the confined microvilli in
outer cells.
Compact morula 32 cells, 10 internal and 22
outer cells
Internal-inner cell mass, outer cell-trophectoderm
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Hatching From the Zona And Implantation of the
Mammalian Blastocyst

• ZP prevent implantation in the oviduct
• Blastocyst secrets strypsin to digest a hole on
  the ZP
• Blastocyst sequeeze out the ZP
• Implantation in the oviduct causes ectopic
  pregnancy

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Cell specification during early development
ICM oct4, nanog, foxd4, fgf4 Trophoblast
eomesodermin
ICM Embryo proper, yolk sac, amnion sac, and
allantois Trophectoderm chorion
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Compariosn of mouse and human trophoblast lineage
derivation
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The expression of Oct4 in d10 bovine embryo
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Gastrulation in mouse
Both birds and mammals are derived from reptilian
species. The Gastrulation pattern of reptilian
for yolky eggs are conserved in both Classes of
animals.
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Inner cell mass-primitive endoderm
epiblast-cup shape
1000 cells
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• Trophectoderm
• A mural
• Trophoblast giant cells
• B polar
• Extraembryonic ectoderm
• Ectoplacental cone

Extra-embryonic structures

• Primitive endoderm
• Parietal endoderm
• Visceral endoderm

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Primitive streak forms at the posterior end Node
is located at the bottom.
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Gastrulation in mouse

• Mesodernal and endodermal cells move through
  streak
• Migrating cells move between ectoderm and
  visceral endoderm
• Embryonic endoderm cells move to replace visceral
  endoderm
• Extraembryonic mesoderm-extraembryonic membranes
• Migrating cells move anterior to form embryonic
  endoderm
• and notochord
• 5. Both notochord and somites form anterior to
  node.
• 6. The embryo is endoderm-mesoderm-ectoderm from
  outside t inside
• 7. Dorsal side is inside the embryo and ventral
  side outside.
• 8. Extra-embryonic mesoderm form at the posterior
  PS.

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Extra-embryonic mesoderm form at the posterior
PS.
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Figure 11.34 Formation of the Notochord in the
Mouse
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Migration through primitive streak

• Cell migration and specification are coordinated
  by FGFs
• No endodermal and mesodermal are formed in
  fgf8-/- mice
• FGF8 down regulate the E-cadherin
• FGF8 control cell specification by regulating
  snail,
• brachyury, and Tbx6.

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The embryo turns to make itself inside of the
extra-embryonic membranes
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Early development in Human
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Figure 11.26 Development of a Human Embryo From
Fertilization to Implantation
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Developing in another organism
Adaptation the formation of placenta Mother
part decidua Fetal tissue chorion---- a.
trophoblast
b. mesoderm derived from ICM
Contact placenta separable contact between fetus
and mother, eg. Pig. Deciduous plancenta
intimate integration between fetus and mother,
eg. Human.
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Figure 11.31 The Derivation of Tissues in Human
and Rhesus Monkey Embryos
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Figure 11.32(1) Tissue Formation in the Human
Embryo Between Days 7 and 11
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Figure 11.32(2) Tissue Formation in the Human
Embryo Between Days 7 and 11
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Figure 11.33(1) Amnion Structure and Cell
Movements During Human Gastrulation
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Figure 11.33(2) Amnion Structure and Cell
Movements During Human Gastrulation
Hypoblast replaced by endodermal cells
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Figure 11.35 Human Embryo and Placenta after 50
Days of Gestation
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Figure 11.36 Relationship of the Chorionic Villi
to the Maternal Blood Supply
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Figure 11.37 The Timing of Human Monozygotic
Twinning withRelation to Extraembryonic Membranes
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Figure 11.38(1) Production of Chimeric Mice
8 cell
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Figure 11.38(2) Production of Chimeric Mice
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Axis formation in the Mouse

• Two signaling center
• Anterior visceral endoderm (AVE)
• Node (organizer)

The node is responsible for the creation of all
of the body. It works Together with AVE to form
the anterior region of the embryo.
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Creation of the two signaling centers in
mammalian embryo
Positions of the two signaling center is
regulated by Interaction between epiblast and
the extraemnryonic membranes
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Mammalian axis formation

• Two signaling center, AVE and node
• AVE formed before the node, induced by
  extrembrypnic
• ectoderm.
• 3. Formation of the node is dependent on the
  trophoblaat
• 4. Arkadia in trophoblast nucleus regulates node
  formation
• 5. Primitive streak forms opposite to the AVE
• 6. AVE expresses head genes (Hesx1, Lim-1, and
  Otx2)
• 7. node express organizer genes (chordin,
  noggin)

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9.5 PC
AVE is responsible for the formation of the
anterior part of The embryo, but it requires the
node to function.
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Axis formation in the Mouse
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Axis formation in the Mouse
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Figure 11.40 Expression of BMP Antagonists in
the Mammalian Node
Chordin Node, anterior PS, axial mesoderm
Chordin-/-
Chordin-/-, noggin-/-
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Temporally and spatially Nodal activity pattern
the A-P axis
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Temporally and spatially Nodal activity pattern
the A-P axis
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Model of Interactions Between the
Visceral Endoderm and Epiblast in Mice
5.0 D
VE rotation
AVE functions to prevent nodal signal, thereby
allowing Anterior genes to be expressed in the
anterior epiblast
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Pattering the anterior-posterior axis
The Hox code hypothesis

• The expressions of the murine Hox genes suggest a
  code
• Whereby certain combinations of Hox genes specify
  a
• particular region of the A-P axis.
• Hox gene properties
• Colinearity
• Posterior dominance

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Evolutionary Conservation of Homeotic Gene
Organization
No one-one correspondence between fly and mammals.
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Evolutionary Conservation of Homeotic Gene
colinear expression
The anterior head, forebrain, mid brain are
specified by Otx and Emc
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Co-linearity the order of the gene on the
chromosome and their spatial and temporal
expression along the
atero-prosterior axis are similar or linear.
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Hox gene expression along the A-P axis of mouse
mesoderm
Hind brain
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Evidences supporting Hox Code hypothesis

• Gene targeting experiments
• Retinoic acid teratogenesis
• Comparative anatomy

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Figure 11.43 Deficient Development of Neural
Crest-Derived Pharyngeal Archand Pouch
Structures in Hoxa-3-Deficient Mice
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Homeotic transformation The conversion of one
body part into another
Posterior dominance more posteriorly Expressed
hox genes tend to inhibit the action of the hox
genes normally expressed anterior to them
The most anterior region is affected by
mutation
Homeotic transformation into anterior
structure
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Figure 11.44 Partial Transformation of the First
Lumbar Vertebra into a ThoracicVertebra by the
Knockout of the Hoxc-8 Gene
Posterior dominance posterior genes show
dominant effects on that of the anterior ones.
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Figure 11.45(1) The Effect of Retinoic Acid on
Mouse Embryos
wildtype
RA treated

• PA fused
• Ossification of skull failed, 3. Limb abnormality

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Figure 11.45(2) The Effect of Retinoic Acid on
Mouse Embryos
RA treated
RA treated
control
Lost of Meckels cartilage
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Comparative anatomy
Chicken Cervical-14 Thoracic-7 Lumbosacral-12/13
Coccygeal-5
Mouse Cervical-7 Thoracic-13 Lumbar-6 Sacral-4 Ca
udal-20
Dose the constellation of Hox gene expression
correlate with the type of vetebra formed or
with the relative position of the vertebrae?
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Hox Hypothesis

• Constellation of Hox genes specify any region
  along
• A-P axis
• 2. Members of a paralogous group may resposible
  for
• different subsets of organs within these
  regions.
• 3. Defects caused by knocking out particular Hox
  genes
• occur in the most antrior region of that
  genes expression.

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Figure 11.46 Mouse and Chick Vertebral Pattern
along the Anterior-Posterior Axis
The Hox CODE DETERMINES THE TYPE OF THE VERTEBRAE
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The Dorsal-Ventral Axis

• Very little is known about the D-V axis
  mechanisms in
• mammals
• ICM cells contacting trophoblast form dorsal axis
• ICM cells exposed to blastocyst fluid become
  hypoblast
• The D-V axis is defined by embryonic-abembryonic
  axis
• embryonic-abembryonic axis is defined by first
  cleavage

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Figure 11.47 Relationship Between the
Animal-Vegetal Axis of the Egg and
theEmbryonic-abembryonic Axis of the Blastocyst
The D-V axis forms at right angles to the A-V
axis of the egg.
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The definition of left and right axis

• Asymmetry of mammalian body
• a. heart
• b. liver
• c. intestine
• d.spleen
• e. scrotum in male
• 2. Global regulation (inversion of embryonic
  turning, inv)
• 3. Organ-specific regulation (situs inversus
  viscerum, iv)

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Figure 11.48 Left-Right Asymmetry in the
Developing Human
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Figure 11.49(1) Situs Formation in Mammals
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Figure 11.49(2) Situs Formation in Mammals
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Mechanisms of situs in mammals

• End effectors are the same but the pathway are
  different
• chicken sonic hedgehog activation
• frog VG1 placement
• Mammal beating of node cilia cells
• 2. Evidences supporting ciliary cells hypothesis
• a. dynein deficient humans have their hearts
  radomized
• b. Iv gene code for dynein
• c. Artificial flow of medium caused reversal
  of situs.