MSK development 1 Flashcards
What are the origins of the post-cranial MSK?
- Axial skeleton (vertebrae/ribs) - somites
- appendicular skeleton (limb digits/girdles) - limb buds
- Axial muscle (vertebral, thoracic, abdominal) - somites
- Appendicular muscles (flexors/extensors) - somites
Axial vs Appendicular
Axial protects things, appendicular moves things
What are somites?
Paraxial mesoderm (either side of axis) that is laid down sequentially cranial to caudal
What are the 4 different differentiated cell populations?
- Sclerotome - vertebrae and ribs (skeleton)
- Myotome - epimere, hypomere, limb muscles (muscles)
- Dermatome - dorsal dermis (skin)
- Syndetome - tendons
What 3 things control somitogenesis and keep it symmetrical?
- Wnt
- FGF
- Retinoic acid gradients
What is ossification?
Bone formation
What is the process of intramembranous ossification?
- 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
What does intramembranous ossification produce?
Flat bones of skull and clavicle
What is endochondral ossification?
- 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
Give an example of a problem that you may have with ossification
- 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
What are the 3 growth axes of limb buds?
- 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)
What happens at week 4 of development?
- 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
What happens at week 6?
- 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
What is it called when fingers do not separate properly due to the blocking of apoptosis?
Syndactyly
What happens at week 7 of development?
- Upper limbs rotate externally (extensors posterior)
- lower limbs rotate internally (extensors anterior)
How is growth regulated at the molecular level?
- 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
What is the zone of polarising activity?
- 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
Summary of hormone regulation
FGFs in the AER activate SSH in ZPA, whilst WNT7a maintains SSH.
- HOX genes regulate types and shapes of bones in the limb
Name 4 limb detects
- Polydactyly
- Cleft hand and foot
- Club foot
- Congenital hip dislocation
What is polydactyly?
- have extra digits
- extra digits frequently lack proper muscle connections
- usually bilateral
What is club foot?
Sole of foot is supinated
- usually accompanies syndactyly
- mainly in males, may be heriditary
What is congenital hip dislocation?
- 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
Epaxial vs Hypaxial
Epaxial = transverse --> spinous process Hypaxial = every other muscle
Innervation overview
- 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
What is a dermatome?
An area of skin supplied by a single spinal nerve
- Dermatomal stripes are different from embryo to adult
Muscle innervation
- nerves innervating segmental muscles divide into dorsal primary ramus (epimere) and ventral primary ramus (hypomere)
- nerves remain with original muscle segment throughout its migration
What is the process of neuromuscular junction formation?
- 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
Myotome overview
- 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
What are the spinal roots for upper and lower limbs?
- Upper limb buds are lower 5 cervical and upper 2 thoracic
- lower limb buds are lower 4 lumbar and upper 2 sacral
What is the molecular regulation of muscle development?
- 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
Muscle regeneration
- Uses muscle stem cells (satellite cells)
- repeats process of embryogenesis
Connective tissue connections
- 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
