1. Chapter 14- Mesoderm-paraxial and intermediate
Fig mesoderm lineages
Recall lineages
Fig. 12.4
Paraxial
Head
Somite
Cartilage,
skeletal,
dermis
Intermediate
Kidney, gonads
Notochord
Lateral
Circulatory,
Body cavity,
extraembryonic
Fig mesoderm lineages in chick
24hr
48hr

2. Chapter 14- Mesoderm-paraxial and intermediate
Head
Somite
Cartilage,
skeletal,
dermis
Paraxial mesoderm
Neural tube
4 components of somite formation
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

3. 4 components of somite formation (cont.)
Paraxial mesoderm
4 components of somite formation (cont.)
3. Axial specification
Paraxial
Distinct somites give rise to distinct structures
Specific hox gene expression predicts the type of vertebra formed
Head
Somite
Cartilage,
skeletal,
dermis
Somites
hox5
hox6
hox9
hox10
Fig 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

4. 4 components of somite formation (cont.)
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

5. 4 components of somite formation 4. Differentiation- (continued)
Paraxial mesoderm
4 components of somite formation
4. Differentiation- (continued)
Paraxial
Somite has three additional regions that follow distinct fates
Head
Somite
1. Dermis
Cartilage,
skeletal,
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 B
Notochord produces sonic hedgehog to influence sclerotome fate

6. Signaling pathway to activate muscle-specific genes
Myogenesis
What dictates the muscle phenotype?
Pax3 is a transcription factor that activates transcription factors Myf5 and MyoD
Wnt?
Pax3
Myf5
+ MyoD
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

7. 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
Mesenchyme
Neural crest cells
Cell clustering
Differentiate into osteocyte (bone cell)
Differentiate into osteoblast (secrete collogen-proteoglycan matrix)

8. Differentiate into osteoblast
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
Human disease- cleidocranial dysplasia (CCD)- due to mutaions in the CBFA1 gene

9. 2. Endochondral ossificationB C A
Pax
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

10. 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

11. Intermediate Mesoderm
Fig 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

12. 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

13. 1. Metanephrogenic mesenchyme formed
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
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