MSK development 1

Question 1

What are the origins of the post-cranial MSK?

Answer 1

• Axial skeleton (vertebrae/ribs) - somites
• appendicular skeleton (limb digits/girdles) - limb buds
• Axial muscle (vertebral, thoracic, abdominal) - somites
• Appendicular muscles (flexors/extensors) - somites

Question 2

Axial vs Appendicular

Answer 2

Axial protects things, appendicular moves things

Question 3

What are somites?

Answer 3

Paraxial mesoderm (either side of axis) that is laid down sequentially cranial to caudal

Question 4

What are the 4 different differentiated cell populations?

Answer 4

• Sclerotome - vertebrae and ribs (skeleton)
• Myotome - epimere, hypomere, limb muscles (muscles)
• Dermatome - dorsal dermis (skin)
• Syndetome - tendons

Question 5

What 3 things control somitogenesis and keep it symmetrical?

Answer 5

• Wnt
• FGF
• Retinoic acid gradients

Question 6

What is ossification?

Answer 6

Bone formation

Question 7

What is the process of intramembranous ossification?

Answer 7

• condensation of mesenchyme into soft sheet permeated with capillaries
• deposition of osteoid tissue by osteoblasts, entrapment of first osteocytes and periosteum formation
• honeycomb of bony trabeculae formed by mineral deposition + creation of spongy bone
• surface filled in by bony deposition - converts spongy bone into compact bone

Question 8

What does intramembranous ossification produce?

Answer 8

Flat bones of skull and clavicle

Question 9

What is endochondral ossification?

Answer 9

• mesenchymal cells in the epiphyses of long bones give rise to hyaline carilage
• primary ossification centre in shaft of bone provides nutients and growth factors via the nutrient artery
• osteoblasts start laying down bone
• medullary cavity is formed by osteoclasts
• secondary ossification centres are made in the epiphyses
• articular cartilage and epiphyseal plate is formed

Question 10

Give an example of a problem that you may have with ossification

Answer 10

• Achondroplastic dwarfism
• “without cartilage formation”
• Have a problem with converting the cartilage to bone
• Results in shortened limb bones as there is premature closure of epiphyseal growth plates

Question 11

What are the 3 growth axes of limb buds?

Answer 11

• proximal to distal (shoulder to fingers) - need to make limbs long
• posterior to anterior (little finger to thumb)
• dorsal to ventral (back to palm of hand)

Question 12

What happens at week 4 of development?

Answer 12

• limb buds are visible - made from mesenchyme from somatic layer of lateral plate + ectoderm (skin) at distal border of limb forms Apical ectodermal ridge (AER)
• as limb grows , cells get further away from AER and differentiate into cartilage and muscle
• limb grows proximally to distally

Question 13

What happens at week 6?

Answer 13

• terminal portion of limb buds flatten to form hand and foot plates
• fingers and toes form (posterior to anterior)
• AER separates into 5 parts due to apoptosis

Question 14

What is it called when fingers do not separate properly due to the blocking of apoptosis?

Answer 14

Syndactyly

Question 15

What happens at week 7 of development?

Answer 15

• Upper limbs rotate externally (extensors posterior)

- lower limbs rotate internally (extensors anterior)

Question 16

How is growth regulated at the molecular level?

Answer 16

• HOX genes - regulate the positioning of the limbs proximal-distally
• BMP - induce formation of AER
• FGF-10 - initiates outgrowth
• After the ridge is established FGF-4/8 maintain the progress zone (rapidly proliferating population of mesenchyme cells adjacent to ridge)
• ZPA - regulates A-P axis

Question 17

What is the zone of polarising activity?

Answer 17

• Cluster of cells at the posterior border of the limb near the flank
• Limit retinoic acid (Vitamin A)
• initiates expression of SHH (regulates the A-P axis)
• As limb grows, ZPA moves distally to remain in proximal to the posterior border of AER

Question 18

Summary of hormone regulation

Answer 18

FGFs in the AER activate SSH in ZPA, whilst WNT7a maintains SSH.
- HOX genes regulate types and shapes of bones in the limb

Question 19

Name 4 limb detects

Answer 19

• Polydactyly
• Cleft hand and foot
• Club foot
• Congenital hip dislocation

Question 20

What is polydactyly?

Answer 20

• have extra digits
• extra digits frequently lack proper muscle connections
• usually bilateral

Question 21

What is club foot?

Answer 21

Sole of foot is supinated

• usually accompanies syndactyly
• mainly in males, may be heriditary

Question 22

What is congenital hip dislocation?

Answer 22

• under-development of acetabulum and head of femur
• dislocation occurs usually after birth - abnormality occur in utero
• most babies with chd are breech deliveries - may interfere with hip joint development

Question 23

Epaxial vs Hypaxial

Answer 23

Epaxial = transverse --> spinous process
Hypaxial = every other muscle

Question 24

Innervation overview

Answer 24

• signals induce nerve growth from the neural tube
• nerve grows and splits sclerotome portion of somite into cranial and caudal
• nerve contacts myotome and dermatome and innervates the segment
• Spinal nerves pass through the intervertebral foramina

Question 25

What is a dermatome?

Answer 25

An area of skin supplied by a single spinal nerve | - Dermatomal stripes are different from embryo to adult

Question 26

Muscle innervation

Answer 26

- nerves innervating segmental muscles divide into dorsal primary ramus (epimere) and ventral primary ramus (hypomere) - nerves remain with original muscle segment throughout its migration

Question 27

What is the process of neuromuscular junction formation?

Answer 27

- growth cone of axon approaches muscle fibre, terminates, differentiates and then starts producing cleft - multiple axons converge - all but one are eliminated - remainder develops a myelin sheath

Question 28

Myotome overview

Answer 28

- small dorsal portion (epimere) formed from dorsomedial cells of somite - forms extensor muscles of vertebral column - larger ventral portion (hypomere) formed from dorsolateral cells of somite - gives rise to muscles of limbs and body wall - Thorax myoblasts form intercostals - Abdomen myoblasts form abdominal muscles and obliques - In limbs, dorsal = extensors, ventral = flexors

Question 29

What are the spinal roots for upper and lower limbs?

Answer 29

- Upper limb buds are lower 5 cervical and upper 2 thoracic | - lower limb buds are lower 4 lumbar and upper 2 sacral

Question 30

What is the molecular regulation of muscle development?

Answer 30

- dorsomedial region migrates ventral - MYF5 forms epimeric musculature - dorsolateral region of somite expresses MYO-D - forms hypomeric musculature - MYOD and MYF5 activate genes myogenin and MRF5 (promotes formation of myotubes and myofibres) - differentiate, fuse and form long multinucleated muscle fibres

Question 31

Muscle regeneration

Answer 31

- Uses muscle stem cells (satellite cells) | - repeats process of embryogenesis

Question 32

Connective tissue connections

Answer 32

- mechanical load also controls skeleton and tendon development - the development of a functional MSK depends on regulation of: cartilage morphogenesis, joint formation, bone morphogenesis and tendon homeostasis