Mesoderm derivatives Gannon

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Mesoderm derivatives (Gannon)

• Major subdivisions of the mesoderm
• Paraxial mesoderm
• Intermediate mesoderm
• Lateral plate mesoderm

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Tissues derived from three germ layers
Skeletal muscle
Heart Vessels
Gonads
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Gastrula fate maps
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Gastrulation in the frog
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Gastrulation in the chick
anterior
posterior
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Gastrulation in the mouse
posterior
anterior
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Five mesodermal regions

• Chordamesoderm (axial mesoderm, dorsal mesoderm)
• Paraxial mesoderm (somitic mesoderm)
• Intermediate mesoderm
• Lateral plate mesoderm
• Head mesoderm (head mesenchyme, prechordal plate)

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Major lineages of vertebrate mesoderm
dorsal
ventral
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Chordamesoderm (Axial/dorsal mesoderm)
This tissues forms the notochord. Major functions
include 1. establishing the anterior-posterior
axis 2. inducing floorplate in overlying neural
tube 3. inducing ventral somitic fates 4.
inducing pancreas outgrowth from gut endoderm
Notochord
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Basic vertebrate body plan
Notochord mesoderm is one of first tissues to
gastrulate
Cells undergo intercalation and elongate along
A/P axis
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Dorsal/ventral patterning of neural tube and
somites pancreas induction
neural tube
somitic mesoderm
endoderm
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Major lineages of vertebrate mesoderm
dorsal
ventral
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Paraxial mesoderm
anterior
Somites

• Somite formation
• Anterior/posterior patterning
• Dorsal/ventral patterning
• Myogenesis

Spinal cord
posterior
Presomitic mesoderm (unsegmented)
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Formation of somites from the unsegmented mesoderm
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Somitogenesis
anterior
posterior
One of the important components of this process
is periodicity.
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The Segmentation Clock
oscillating wave of gene expression in presomitic
mesoderm
New cells continue to be added to posterior by
gastrulation
A new somite forms from the unsegmented mesoderm
every 90 minutes
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Genes involved in this process
Notch/Delta
Hairy transcription factor
Eph receptors/ephrins
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Notch signaling and segmentation of somites
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Eph signaling and segmentation of somites
Somites
anterior
posterior
EphA4
ephrin B2
Presomitic mesoderm
Ephrin ligand is turned on only as the somite
gets ready to bud off unsegmented plate
Eph receptor is expressed in youngest somites and
is extinguished as somites mature
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The ventral part of somites gives rise to
vertebrae. Vertebrae differ along the A/P axis.
cervical
thoracic
lumbar
sacral
caudal
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Question
How could you test whether and when somite fate
becomes determined along the A/P axis?
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Patterning of somites along anterior/posterior
axis
Result suggests that somites have an
anterior/posterior identity
before they even leave the unsegmented plate
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Hox genes are involved in this process
Axial identities are determined by the
combinatorial expression of homeotic selector
genes of the Hox class, with fixed Hox codes
for somites residing at anatomical
landmarks. (Burke et al., 1995, Development)
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What is the Hox code?
Expression pattern suggests that the most
posteriorally expressed HOX gene will define a
new identity.
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Indeed, loss of Hoxc8 results in
anteriorization of first lumbar vertebra to
thoracic with rib attached
This is called a homeotic transformation
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Question
How might you posteriorize a cervical vertebra?
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Patterning of somites along dorsal/ventral axis
Somite derivatives include

• Dorsal dermis of skin
• Medial/lateral muscles of the rib cage, back,
  limbs and body wall, and tongue
• Ventral vertebral and rib cartilage

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Somitogenesis
anterior
posterior
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Somite derivatives include
Dorsal dermis of skin dermatome
dermomyotome
Medial/lateral muscles myotome
Ventral axial skeleton sclerotome
hypaxial
epaxial
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Dorsal/Ventral Patterning of the Somites
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Genes involved in this process
hypaxial
epaxial
Unlike anterior/posterior patterning of somites,
commitment of cells within a somite along the
dorsal/ventral axis occurs after somite
formation. Thus, somites can be rotated and
development proceeds as normal.
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Myogenesis
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Myogenesis
Myogenic bHLH transcription factors (MRFs)
include MyoD, Myf5, MRF4
Pax3 is also involved in migration and
differentiation of limb muscle
Skeletal muscle becomes multinucleate by the
fusion of cells.
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10 minute break!
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Major lineages of vertebrate mesoderm
dorsal
ventral
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Intermediate mesoderm

• Generation of the urogenital system
• Development of the kidney
• Reciprocal inductive interaction of kidney
  tissues

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Development of the urogenital system in the mouse
The intermediate mesoderm generates the kidneys,
the gonads, and their respective duct systems.
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Development of the mammalian kidney
Induction of branching
Induction of condensation
Transition from mesenchymal to epithelial
organization
Fusion
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Ureteric bud growth and branching
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Reciprocal induction between mesenchyme and
epithelium during kidney development
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Major lineages of vertebrate mesoderm
dorsal
ventral
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Lateral plate mesoderm

• Splanchnic versus somatic LPM
• Formation of the heart
• Formation of blood vessels

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Splitting of lateral mesoderm in chick
Somatic generates lining of body wall
Splanchnic generates heart, blood vessels, blood
cells, muscles covering digestive organs
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Splitting of lateral mesoderm in frog
somatic
somatic
splanchnic
splanchnic
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Origin and fate of heart forming cells
cardiogenic mesoderm
outside cardiac field
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Specification of cardiac precursor cells
Fusion of heart fields at midline
Anterior-medial migration
specification
gastrulation
Signals from endoderm specify location of heart
field
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Location of cardiac precursor cells
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Questions
How could you analyze when heart primordia are
specified to give rise to atrial versus
ventricular myocytes? How would you test when
they become determined?
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Fusion of heart primordia in chick embryo
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Migration of heart primordia
chick
fish
cardia bifida
miles apart mutant
surgical inhibition of fusion
genetic inhibition of migration
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Questions
How might you determine whether the miles apart
gene product acts cell autonomously or non-cell
autonomously?
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Cardiac looping and chamber formation
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Vascular development
PECAM labeling of endocardium and vessel
endothelial cells
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Origin and fate of hemangioblast cells
Blood vessels and blood cells are believed to
share a common precursor, the hemangioblast.
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Vasculogenesis and angiogenesis
Vasculogenesis formation of new vessels de novo
Angiogenesis formation of vessels from existing
vessels, remodeling of existing vessels
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Specification of arteries vs. veins
It was previously thought that the identities of
arteries and veins arose in response to
hemodynamic forces.
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Notch signaling in blood vessel formation
Arteries higher levels Notch receptor signaling
Veins higher levels of ligands
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Eph signaling in blood vessel formation
Arteries ephrin ligand B2
Veins Eph receptor B4