Transcript Chapter 14- Mesoderm-paraxial and intermediate

Chapter 14- Mesoderm-paraxial
and intermediate
Fig. 14.1- mesoderm lineages
Recall lineages
Notochord
Intermediate
Fig. 12.4
Kidney,
gonads
Paraxial
Circulatory,
Head Somite
Body cavity,
extraembryonic
Cartilage,
skeletal,
dermis
24hr
48hr
Lateral
Fig. 14.2- mesoderm
lineages in chick
Chapter 14- Mesoderm-paraxial
and intermediate
Paraxial
Paraxial mesoderm
4 components of somite formation
Neural tube
Head
1. Periodicity• somites form from cell groupings
in regular intervals
Somite
Cartilage,
skeletal,
dermis
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
Paraxial mesoderm
4 components of somite formation (cont.)
3. Axial specification
•Distinct somites give rise to distinct structures
•Specific hox gene expression predicts the type
of vertebra formed
Paraxial
Head
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
Somite
Cartilage,
skeletal,
dermis
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
Paraxial mesoderm
4 components of somite formation
4. Differentiation- (continued)
Paraxial
Somite has three additional regions that follow distinct fates
Head
Cartilage,
skeletal,
dermis
1. Dermis
A
2. Back muscles
3. Body wall
Muscles
Somite
Fig. 14.9
Sclerotome
B
A Neural tube produces NT-3 and Wnt proteins that influence somite cell fate
B Notochord produces sonic hedgehog to influence sclerotome
fate
Myogenesis
What dictates the muscle phenotype?
Pax3 is a transcription factor that activates transcription factors
Myf5 and MyoD
Wnt?
Pax3
Myf5
+ MyoD
MyoD binding site
Muscle-specific genes
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
Osteogenesis (Bone development)
What dictates the bone development?
There are three lineages that produce bone1) Somites (vertebrae/ribs)
2) Lateral mesoderm (limbs)- Not yet discussed
3) Cranial Neural crest (head/face)
Osteogenesis occurs by two mechanisms
1) Intramembrane ossification- bone withour cartilage precursor
2) Endochondral ossification- cartilage converted to bone
1. Intramembrane ossification
Mesenchyme
Neural crest cells
Differentiate into
osteocyte (bone cell)
Cell clustering
Differentiate into osteoblast
(secrete collogenproteoglycan matrix)
1. Intramembrane ossification (cont.)
Mechanism of intramembranous ossification)
Transcription factor CBFA1 plays a key role
BMP proteins also are important
Mesenchyme
WT
CBFA1
CFB1A -/-
Differentiate into osteoblast
Activates expression of several
bone-specific genes
CFBA1 KO- all
ossification prevented
Blue- cartilage
Red- Bone
Fig. 14.12
Human disease- cleidocranial dysplasia
(CCD)- due to mutaions in the CBFA1 gene
2. Endochondral ossification
Pax B
A
cartilage
Mesenchyme
E
Proliferation
ceases, matrix
is modified
Blood vessels
invade,
Chondocytes die
A
B
C
D
Fig. 14.13
E
C
Differentiate into chondrocytes
D
Proliferate and form model of bone
by producing an EM
Adjacent cells
(not
chondrocytes)
differentiate into
osteoblasts to fill
in bone
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
Intermediate Mesoderm
Fig. 14.1- mesoderm lineages
Recall lineages
Intermediate
Fig. 12.4
Kidney,
gonads
Paraxial
Lateral
Circulatory,
Head Somite
Body cavity,
extraembryonic
Cartilage,
skeletal,
dermis
Kidney development
Three stages
1. Pronephric duct arises from intermediate
mesoderm just ventral to anterior somites
and migrate toward head
Kidney development
Three stages
1. Pronephric duct arises from intermediate
mesoderm just ventral to anterior somites
and migrates toward tail
2. Migrating nephric duct cells induce
mesenchyme to form pronephros (tubules)
Pronephros
Nephric
Duct
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
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
4. ureteric bud secretes LIF to
induce mesenchyme cells to
aggregate and become epithelial
5. Metanephrogenic mesenchyme
induces branching of ureteric bud
6. Differentiation and growth of the
ureteric bud.