Musculoskeletal Development

Question 1

Somites:
Where do they form?

What do they form?

What determines what each somite becomes?

What are the 4 groups of Mesoderm that it splits into? What does each group form?

Answer 1

• From Presomitic Mesoderm (PSM); grows from cranial to caudal end of embryo
• Axial Skeleton (vertebrae, ribs), Axial muscles (vertebral, thoracic, abdominal), Appendicular muscles (flexor, extensors in limbs)
• Hox genes
• • Chorda-mesoderm; Notochord
  • Paraxial mesoderm; becomes PSM, which further differentiates into the Sclerotome, Myotome, and Dermatome
  o Sclerotome; Vertebrae and ribs
  o Dermomyotome; Myotome (Epimere, Hypomere, Limb muscles), Dermatome (Dorsal dermis)
  o Syndetome; Tendons
  • Intermediate mesoderm; Kidney, Gonads
  • Lateral mesoderm; Appendicular skeleton

Question 2

How do the Somites cause spinal nerve formation from the neural tube?

Why do spinal nerves pass between vertebrae?

How is somite differentiation controlled?

Answer 2

• Grows between Sclerotome to innervate the Myotome and Dermatome = Segmental pattern of innervation
• As spinal nerve grows, it splits the sclerotome into cranial and caudal halves; Cranial and caudal halves of adjacent sclerotomes (vertebrae) fuse together to form a vertebral body (LOOK AT PICTURE)
• Signalling molecules released by Notochord, Neural tube, Lateral plate mesoderm

Question 3

What are the 2 models that determine the way in which the somites form and divide? What’s the function of both?

Answer 3

1. Clock mechanism marks time; found in PSM cells
   o Oscillations of the clock are made by delayed negative feedback on gene expression
2. Trigger mechanism tells PSM when to form somites
   o Made by opposing gradient thresholds of signalling molecules

Question 4

Limbs:
What are they formed from?

How are they formed?

Answer 4

• Limb Buds and develop from LATERAL MESODERM (appendicular skeleton)
• • Migration of muscle precursors from myotome of somite into limb bud
  • Splitting of muscle in bud in dorsal and ventral muscle masses
  • Signals from limb induce the myoblasts to migrate

Question 5

Dermatome (Dorsal Dermis):
What is it in an embryo?

What is it in an adult?

Why does it have a segmental pattern in the limb bud?

How does the pattern change as the limb bud grows? Why?

Answer 5

• Subdivision of a dividing somite
• Area of skin supplied by a single spinal nerve
• Comes from Dermomyotome and the adjacent spinal nerves at the
  somite is what will provide its sensory innervation
• Segmental pattern converts into a proximo-distal pattern as limbs rotate during development

Question 6

Sclerotome:
What do the 5 most cranial somites form?

What does it do to become the vertebrae?

What happens to the Notochord?

What is the skeleton like throughout it’s development?

Describe 3 abnormalities of the Sclerotome

Answer 6

• Occipital bone
• Sclerotomes surround the Notochord, Proliferate rapidly, and then Condense around the neural tube; take shape of a vertebrae
• Degenerates along with most of cord, forming the Nucleus Pulposus
• Initially formed as cartilage (Chondrification) before mineralising to form bone (Endochondral Ossification)
• • Abnormal segmentation; Fused vertebrae, Scoliosis
  • Klippel-Feil syndrome - Short neck as ↓number of cervical vertebrae
  • Spina Bifida Occulta - failed fusion of vertebral arches

Question 7

Myotome:
What does it form?

What does it divide into? What do they both form? What are they innervated by?

What is the muscle pattern dictated by?

What are the 4 stages it takes to become a Myofibre?

Answer 7

• Back and Limb muscles, Ventral body wall
• • Epimere; small dorsal portion; Extensor muscles of spine, Innervated by Dorsal ramus of spinal nerve
  • Hypomere; large ventral portion; Limb and body wall muscles, Innervated by Ventral ramus of spinal nerve
• Connective tissue
• 1. Myoblast; myotome migrates to muscle location and proliferates
     
     2. Primary Myotube; initial myoblast fusion
     3. Secondary Myotube; later myoblast proliferation and fusion
     4. Myofibre; innervation and expression of contractile proteins

Question 8

What cells are used for muscle regeneration?

What do these cells express?

How do they form new myofibres?

Answer 8

• Satellite cells; muscle resident stem cells
• Pax7
• When activated, they follow the same process as myotomes during muscle development

Question 9

What are the 4 stages that occur for the formation of a Neuromuscular Junction?

Answer 9

1. Growth cone of axon approaches muscle fibres and forms contact
2. On contact, axon differentiates and the basal lamina appears in the cleft
   o Specialised extracellular matrix forms in the cleft
3. Multiple axons converge; Ach receptors are laid down on the muscle surface and the axons compete
4. One axon wins and becomes myelinated; ↑AChR density and elaboration of the post-synaptic membrane

Question 10

Chrondogenesis defects:
Features of Achondroplasia?
Feature of Brevicollis?

Limb defects:
Feature of Amelia?
Feature of Polydactyly?
Feature of Ectrodactyly?
Feature of Syndactyly?

Answer 10

• Dwarfism, Lack of cartilage conversion into bone
• Short neck
• Total absence of a limb
• Extra fingers
• Split/cleft hand
• Fusion of fingers