Musculoskeletal Development 1: somites and bones (S3) Flashcards
What is a somite?
One of the paired masses of paraxial mesoderm, distributed along the sides of the neural tube, that will eventually become dermis, skeletal muscle, or vertebrae.
Which of the following don’t come from somites? What do they originate from?
- Axial skeleton
- Appendicular skeleton
- Axial muscles
- Appendicular muscles
The appendicular skeleton doesn’t come from somites but it comes from the limb buds
In what direction are somites laid down?
Sequentially cranial to caudal
What is the mesoderm found lateral to the neural tube called?
The paraxial mesoderm
What 4 compartments do somites separate into?
- Dermatome (dorsal dermis)
- Myotome (epimere, hypomere, limb muscles)
- Sclerotome (vertebrae and ribs)
- Syndentome (tendons)
How often are somites produced?
Every 4 hours
What gene substances regulate somite formation and where are they expressed?
- Wnt
- FGF (fibroblast growth factor)
- Retinoic acid
Expressed in pre-somitic mesoderm, during somite formation they each develop an ‘identity’.
What is the syndentome?
The progenitor to tendons, lie between the sclerotome and myotome
What is intramembranous ossification?
Form the flat bones of the skull, the dermis differentiates directly into bone without a cartilage stage.
Osteoblasts -> osteoid -> maturation -> mineralisation -> remodelling/resorption etc.
What is endochondral ossification?
Mesenchymal cells give rise to hyaline cartilage model -> becomes ossified, occurs in foetal devpt.
Week 12 - give rise to diaphysis -> skeletal maturity
What is the precursor to all connective tissue?
Mesenchyme
What are the 3 main types of cartilage?
- Hyaline (trachea, nose, ribs) - fluid, vascular, neural, acellular
- Fibrous (pubic symphysis, meniscus, intervertebral)
- Elastic (ear, nose)
What is achondroplastic dwarfism?
Literally “without cartilage formation” - occurs when there are defects in FGF signalling or issues in chondrocyte proliferation.
Problem is not in cartilage formation but in converting it to bone.
Results in shortened limb bones due to premature closure of epiphyseal growth plates - child like limbs with adult sized akial skeleton.
What is the first stage of limb formation?
Limb buds are initiated
What are the 3 axes of limb bud patterning?
- Proximal -> distal (shoulder to fingers)
- Posterior -> anterior (little finger to thumb)
- Dorsal -> ventral (back to palm of hand)
When are limb buds visible in foetal development?
Week 4
What are the limb buds made of?
Mesenchyme from somatic layer of lateral plate (located laterally to neural tube).
What does the ectoderm at the distal border of the limbs form?
Apical Ectodermal Ridge (AER) - it’s at the ends, allows our arm to grow, cells grow further from the ridge, differentiation between cartilage, bones, muscle and skin occurs.
What happens at week 6 of limb formation?
Terminal portion of limb buds flatten to form handplates and footplates.
Fingers and toes form (posterior to anterior) when AER separates into 5 parts due to cell death.
How do our digits separate?
- Digital rays of condensed mesenchyme present in handplate
- Notches between rays as mesenchyme breaks down
- Breakdown due to apoptosis
- Blocking of apoptosis leads to syndactyly
Do upper and lower limbs develop at the same time?
Lower limbs approx 1-2 days behind upper limb
How do our upper and lower limbs rotate at week 7 and why?
- Upper limbs rotate externally as extensors posterior
- Lower limbs rotate internally as extensors anterior
What are HOX genes important for?
Regulate positioning of limbs proximal-distally
After proximal-distal positioning, what initiates outgrowth?
FGF-10
What is the role of bone morphogenic proteins?
Initiate formation of apical ectodermal ridge
Which genes maintain the Progress Zone after the ridge is established?
FGF-4 and FGF-8
What is the Progress Zone?
Rapidly proliferating population of mesenchyme cells adjacent to ridge.
What is the Zone of Polarising Activity?
Cluster of cells at the posterior border of limb near the flank/body wall.
Procludes retinoic acid (Vit A) -> initiates expression of sonic hedgehog (SHH) factor that regulates A-P axis
ZPA moves distal as limb grows.
Where are the signalling molecules that pattern the limb produced?
AER and ZPA
When during development is most sensitive for teratogen induced limb malformations?
4-5th weeks - eg. thalidomide
What is polydactyly?
Extra digits frequently lack proper muscle connections - abnormalities with excessive numbers of bones are mostly bilateral.
Absence of digit such as thumb (ectrodactyly) usually unilateral.
What is the difference between syndactyly, polydactyly and ectrodactyly?
- Syndactyly - When digits joined together
- Polydactyly - Extra digits
- Ectrodactyly - Missing digits
What is cleft hand/foot?
Abnormal cleft between 2nd-4th metacarpal bones and soft tissues, 3rd metacarpal/phalanx almost always absent.
What is clubfoot?
Usually accompanies syndactyly, sole of foot is turned inward, foot is aducted and plantar flexed. Mainly in males and may be hereditary.
What is congenital hip dislocation?
Underdevelopment of acetabulum and head of femur.
Common in females, dislocation occurs after birth, abnormality occurs in utero.
