Chapter 14- Mesoderm-paraxial and intermediate

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Chapter 14- Mesoderm-paraxial and intermediate
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Chapter 14- Mesoderm-paraxial and intermediate
Paraxial mesoderm
4 components of somite formation

1. Periodicity-

• somites form from cell groupings in regular
  intervals

Fig. 14.3

• total number of somites is 50 in chicks, 65 in
  mice

• Mechanism? Involves the hairy gene
• Hairy gene expression correlates with
  positioning of somites
• This effect is independent of all surrounding
  tissue

2. Epithelialization- mesenchyme is converted to
epithelium prior to final somite formation

• EM proteins fibronectin and N-cadherin link
  cells into clustered units

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Paraxial mesoderm
4 components of somite formation (cont.)
Paraxial
3. Axial specification

• Distinct somites give rise to distinct structures

Head
Somite

• Specific hox gene expression predicts the type of
  vertebra formed

Cartilage, skeletal, dermis
Somites
hox5
hox6
hox9
hox10
Fig. 11.40-Mouse somites mapped to vertebrate
regions and to specific hox gene expression
4. Differentiation- somites form 1) cartilage of
vertabrae and ribs, 2) muscles of rib cage, limbs
and back, and 3) dermis of the dorsal skin
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Paraxial mesoderm
4 components of somite formation (cont.)
Paraxial
4. Differentiation (cont)- somites form 1)
cartilage of vertabrae and ribs 2) muscles of
rib cage, limbs and back 3) dermis of the dorsal
skin
Head
Somite
Cartilage, skeletal, dermis
Fig. 14.7
Some somite cells become mesenchymal cells again
to form sclerotome- these will become cartilage
of vertebrae and ribs
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Paraxial mesoderm
4 components of somite formation
4. Differentiation- (continued)
Paraxial
Somite has three additional regions that follow
distinct fates
Head
Somite
Cartilage, skeletal, dermis
1. Dermis
A
2. Back muscles
Fig. 14.9
3. Body wall Muscles
B
Sclerotome
A
Neural tube produces NT-3 and Wnt proteins that
influence somite cell fate
Notochord produces sonic hedgehog to influence
sclerotome fate
B
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Myogenesis
What dictates the muscle phenotype?
Pax3 is a transcription factor that activates
transcription factors Myf5 and MyoD
Pax3
Wnt?
MyoD
Myf5
Muscle-specific genes
MyoD binding site
Signaling pathway to activate muscle-specific
genes (Fig. not in text)
Introduction of MyoD into other cell types
converts them to muscle
Myoblasts fuse to form myotubes to produce muscle
fibers
Fig. 14.10
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Osteogenesis (Bone development)
What dictates the bone development?

• There are three lineages that produce bone-
• Somites (vertebrae/ribs)
• Lateral mesoderm (limbs)- Not yet discussed
• Cranial Neural crest (head/face)

• Osteogenesis occurs by two mechanisms
• Intramembrane ossification- bone withour
  cartilage precursor
• Endochondral ossification- cartilage converted to
  bone

1. Intramembrane ossification
Neural crest cells
Mesenchyme
Cell clustering
Differentiate into osteoblast (secrete
collogen-proteoglycan matrix)
Differentiate into osteocyte (bone cell)
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1. Intramembrane ossification (cont.)
Mechanism of intramembranous ossification)
Transcription factor CBFA1 plays a key role
BMP proteins also are important
CBFA1
Mesenchyme
Differentiate into osteoblast
Activates expression of several bone-specific
genes
WT
CFB1A -/-
CFBA1 KO- all ossification prevented
Blue- cartilage Red- Bone
Fig. 14.12
Human disease- cleidocranial dysplasia (CCD)- due
to mutaions in the CBFA1 gene
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2. Endochondral ossification
B
C
Pax
A
cartilage
Differentiate into chondrocytes
Mesenchyme
E
D
Proliferation ceases, matrix is modified
Blood vessels invade, Chondocytes die
Proliferate and form model of bone by producing
an EM
Adjacent cells (not chondrocytes) differentiate
into osteoblasts to fill in bone
A
B
C
D
E
Fig. 14.13
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Osteoclasts are cells which hollow out bones to
form cavities

• Osteoclasts enter through blood vessels

• Osteoclasts are likely form blood-lineage
  precursors

The disease ostroporosis occurs if too much
osteoclast activity- bones become brittle
The disease ostropetrosis occurs if too little
osteoclast activity- bones are not hollowed out
enough
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Intermediate Mesoderm
Fig. 14.1- mesoderm lineages
Recall lineages
Lateral
Intermediate
Paraxial
Circulatory, Body cavity, extraembryonic
Kidney, gonads
Head
Somite
Fig. 12.4
Cartilage, skeletal, dermis
Kidney development
Three stages
1. Pronephric duct arises from intermediate
mesoderm just ventral to anterior somites and
migrate toward head
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Kidney development
Three stages
1. Pronephric duct arises from intermediate
mesoderm just ventral to anterior somites and
migrates toward tail
Pronephros
Nephric Duct
2. Migrating nephric duct cells induce mesenchyme
to form pronephros (tubules)
3. Pronephric tubules degenerate, but a new set
of mesonephros tubules are formed (approx 30 in
humans) further down
The mesonephros produces hematopoietic stem cells
and, in some mammals, become sperm carrying tubes
The metanephros tubules are formed from
mesenchyme, which induces ureteric buds (these
become ureters that transport urine from bladder)
Fig. 14.18
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Ureteric bud and metanephrogenic mesenchyme
interact to become the kidney- called reciprocal
induction
Mechanism of reciprocal induction
1. Metanephrogenic mesenchyme formed
2. Metanephrogenic mesenchyme secretes GDNF and
HGF to induce ureteric bud form
Fig. 14.19
3. Ureteric bud secretes FGF2 and BMP2 to prevent
apoptosis of Metanephrogenic mesenchyme
5. Metanephrogenic mesenchyme induces branching
of ureteric bud
6. Differentiation and growth of the ureteric
bud.
4. ureteric bud secretes LIF to induce mesenchyme
cells to aggregate and become epithelial