Musculoskeletal Development 1: somites and bones (S3)

Question 1

What is a somite?

Answer 1

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.

Question 2

Which of the following don’t come from somites? What do they originate from?

• Axial skeleton
• Appendicular skeleton
• Axial muscles
• Appendicular muscles

Answer 2

The appendicular skeleton doesn’t come from somites but it comes from the limb buds

Question 3

In what direction are somites laid down?

Answer 3

Sequentially cranial to caudal

Question 4

What is the mesoderm found lateral to the neural tube called?

Answer 4

The paraxial mesoderm

Question 5

What 4 compartments do somites separate into?

Answer 5

• Dermatome (dorsal dermis)
• Myotome (epimere, hypomere, limb muscles)
• Sclerotome (vertebrae and ribs)
• Syndentome (tendons)

Question 6

How often are somites produced?

Answer 6

Every 4 hours

Question 7

What gene substances regulate somite formation and where are they expressed?

Answer 7

• Wnt
• FGF (fibroblast growth factor)
• Retinoic acid

Expressed in pre-somitic mesoderm, during somite formation they each develop an ‘identity’.

Question 8

What is the syndentome?

Answer 8

The progenitor to tendons, lie between the sclerotome and myotome

Question 9

What is intramembranous ossification?

Answer 9

Form the flat bones of the skull, the dermis differentiates directly into bone without a cartilage stage.

Osteoblasts -> osteoid -> maturation -> mineralisation -> remodelling/resorption etc.

Question 10

What is endochondral ossification?

Answer 10

Mesenchymal cells give rise to hyaline cartilage model -> becomes ossified, occurs in foetal devpt.

Week 12 - give rise to diaphysis -> skeletal maturity

Question 11

What is the precursor to all connective tissue?

Answer 11

Mesenchyme

Question 12

What are the 3 main types of cartilage?

Answer 12

• Hyaline (trachea, nose, ribs) - fluid, vascular, neural, acellular
• Fibrous (pubic symphysis, meniscus, intervertebral)
• Elastic (ear, nose)

Question 13

What is achondroplastic dwarfism?

Answer 13

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.

Question 14

What is the first stage of limb formation?

Answer 14

Limb buds are initiated

Question 15

What are the 3 axes of limb bud patterning?

Answer 15

• Proximal -> distal (shoulder to fingers)
• Posterior -> anterior (little finger to thumb)
• Dorsal -> ventral (back to palm of hand)

Question 16

When are limb buds visible in foetal development?

Answer 16

Week 4

Question 17

What are the limb buds made of?

Answer 17

Mesenchyme from somatic layer of lateral plate (located laterally to neural tube).

Question 18

What does the ectoderm at the distal border of the limbs form?

Answer 18

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.

Question 19

What happens at week 6 of limb formation?

Answer 19

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.

Question 20

How do our digits separate?

Answer 20

• 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

Question 21

Do upper and lower limbs develop at the same time?

Answer 21

Lower limbs approx 1-2 days behind upper limb

Question 22

How do our upper and lower limbs rotate at week 7 and why?

Answer 22

• Upper limbs rotate externally as extensors posterior
• Lower limbs rotate internally as extensors anterior

Question 23

What are HOX genes important for?

Answer 23

Regulate positioning of limbs proximal-distally

Question 24

After proximal-distal positioning, what initiates outgrowth?

Answer 24

FGF-10

Question 25

What is the role of bone morphogenic proteins?

Answer 25

Initiate formation of apical ectodermal ridge

Question 26

Which genes maintain the Progress Zone after the ridge is established?

Answer 26

FGF-4 and FGF-8

Question 27

What is the Progress Zone?

Answer 27

Rapidly proliferating population of mesenchyme cells adjacent to ridge.

Question 28

What is the Zone of Polarising Activity?

Answer 28

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.

Question 29

Where are the signalling molecules that pattern the limb produced?

Answer 29

AER and ZPA

Question 30

When during development is most sensitive for teratogen induced limb malformations?

Answer 30

4-5th weeks - eg. thalidomide

Question 31

What is polydactyly?

Answer 31

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.

Question 32

What is the difference between syndactyly, polydactyly and ectrodactyly?

Answer 32

• Syndactyly - When digits joined together
• Polydactyly - Extra digits
• Ectrodactyly - Missing digits

Question 33

What is cleft hand/foot?

Answer 33

Abnormal cleft between 2nd-4th metacarpal bones and soft tissues, 3rd metacarpal/phalanx almost always absent.

Question 34

What is clubfoot?

Answer 34

Usually accompanies syndactyly, sole of foot is turned inward, foot is aducted and plantar flexed. Mainly in males and may be hereditary.

Question 35

What is congenital hip dislocation?

Answer 35

Underdevelopment of acetabulum and head of femur.

Common in females, dislocation occurs after birth, abnormality occurs in utero.