Chrondogenesis Flashcards
What 3 embryonic places to bone’s originate from and what bones do they form?
- Cranial neural crest (craniofacial skeleton)
- Somite’s (axial skeleton)
- Lateral mesoderm (limb skeleton)
What is the Axial skeleton and why do all the parts of it consist of different shapes and sizes?
bit in the middle so the ribs, vertebral column which forms from the paraxial mesoderm
- all come from the same cells but have diff sizes due to hox genes defining the A-P axis
- Hox also controls proliferation controlling size
What are the three steps leading to axial skeleton formation?
- Sclerotome induction
- Cartilage formation = chrondogenesis
- Ossification of axial skeleton = osteogenesis (formation of bone)
What is the slightly more detailed sequence of events leading to axial skeleton formation?
Stem cell in somite
Scelrotomal cells
Chrondoblasts
Chrondocytes
Hypertorphic chrondocytes
What precursors are found in the sclerotome?
sclerotome located on medial side of each somite adjacent to notochord
dorsal = pax3/7 for predetermined skeletal muscles
pax7= specifically for muscle repair
pax 1/9 involved in axial skeletal specification (similar structure to pax3/7)
Where is pax 1/9 expressed?
- Both in ventral part of somite where sclerotome arises
- Pax1 expressed more medially, pax9 expressed more laterally
What happens when you KO pax1, pax9 and then both?
Pax 1 KO:
- mice are viable with some defects but otherwise fairly normal
Pax9 KO:
- mouse dies after birth as they have craniofacial and limb impairments
- little defect in axial skeleton!
Both KO:
- mice completely lack vertebral bodies, vertebral discs and ribs
- functional redundancy
What are the signals controlling sclerotome formation?
- Neural tube, notochord, ectoderm and lateral plate mesoderm contribute signals leading to specification of the sclerotome
- Shh from ventral and BMP4 from lateral plate prevent Pax1 from expanding into the lateral domain, this is how you restrict the domain
How do we see if these sclerotome signals are the right ones for differentiation?
Ectopic signalling (GOF)
LOF removing SHH receptors etc.
How do chrondoblasts form?
- Once you have specified cells in the sclerotome they will migrate laterally and will surround the notochord
- Downregulation of Pax1/9
- Condensation of cells
- Forms chrondoblast which proliferate induced by BMP family
How does a chrondocyte form?
- Production of cartilage matrix through proliferation of chrondoblast requires Sox9
- Leads to final differentiated cartilage cell - a chrondocyte
What are the two main modes of ossification?
- Intramembranous ossification: mainly used for ossification of bones from skull
- Endochondral ossification : used for ossification of most bones (limb)
How does Endochronal ossification occur?
- Chronogenesis forms cartilage
- Chondrocytes stop dividing and become hypertrophic (enlargement)
- Triggers arrival of blood vessels to areas where chondrocytes have undergone apoptosis to form bone marrow
- Osteoblasts replace disappearing cartilage and form primary ossification centre (main shaft of bone)
- Secondary ossification centres are formed in epiphyses leaving a cartilage plate (growth plate) between epiphysis (rounded bit) and diaphysis
How do you regulate the production of cartilage with the production of bones?
- Some bones form directly from the conversion of mesenchymal cells into osteoblasts and those subsequently differentiate into osteocytes
- In the case of the axial skeleton you first form a cartilage and THEN the bone comes when you have the full model of the cartilage
What is Campomelic dysplasia? (CD)
- mutation in Sox 9 shows defect with short bones because there are issues with proliferation and formation of cartilage model
- Shows Sox9 is essential for subsequent proliferation of chondroblasts into chondrocytes
