L7.1 Myogenesis

Question 1

What is myogenesis?

Answer 1

• Myogenesis → synthesis of new muscles

Question 2

How is a muscle cell defined?

Answer 2

• Each muscle fibre is a single muscle cell

Question 3

What are somites and their different differentiations?

Answer 3

• Somites → myotome → all skeletal muscles from neck down (except for some head and neck muscles - eg tongue)
  
  • Med → axial trunk muscles
  • Lat → limb muscles
  • Head mesoderm → head & jaw muscles
  • Lat occipital mesoderm → neck muscles

Question 4

Why is a muscle cell a syncytium?

Answer 4

• A muscle cell is a Syncytium : large mass of cytoplasm separated into individual cells & contain many nuclei

Question 5

What are the stages of embyonic development to a muscle fibre?

Answer 5

Question 6

Muscle progenitor cells (MPC)

Answer 6

• Pax3, 7
• Multipotent
• Express genes → specialised into myoblaasts (committed, but still highly proliferative)

Question 7

Myoblasts

Answer 7

• pax 3, 7, MyoD
• Highly prolif
• Spindle shaped
• 1 centrally located nucleus

Question 8

Myotube

Answer 8

• MyoD, Myogenin, SRF
• Terminally differentiated (x prolif)
• Central nuclear chain (many nuclei)
• Can contract but lack specialised structures of muscle fibres

Question 9

Mature myofibre

Answer 9

• Myogenin, MHC
• Nuclei move to periphery
• Specalised structures develop (eg t-tubules)

Question 10

Regulation: transcription factors

Answer 10

• Pax 3, 7
  
  • Specify differentiation of embryonic stem cells into MPC
    
    • BMP4 control expression of Pax 3 & 7
  • Pax 3 & 7 highly homologous → ONLY overlapping during myogenic specification
  • But dring embryo dev:
    
    • X pax 3 → x limb muscles
    • X pax 7 → normal embryonic myogenesis, but x satellite cells
    • X pax 3 & 7 → complete absence of musculatur

Question 11

Regulation: Myogenic regulatory Factors (MRF)

Answer 11

• basic helix-loop helix family
• Primary: MyoD, Myf5
  
  • Expressed early in muscle dev
  • Vital to myogenesis, but redundant with each other
  • Promote expression of myogenin → begin differentiation
• Secondary: Myogenin, MRF 4
  
  • Expressed during differentiation
  • Promote further differentiation & specialisation
  • Both important (cannot take either out), not redundant with each other
  • Promote expression of muscle specific genes (eg MyHC)

Question 12

MEF 2 & SRF

Answer 12

• essential for muscle differentiation (from myotubes → mature myofibres), but are not MRFs
• Cannot initiate myogenesis, but contributes to differentiation & maturation

Question 13

Regulation: Growth factors

Answer 13

Proliferation Differentiation

IGF-1 ↑ ↑

LIF, IL-6 ↑ ↔

FGF, HGF ↑ ↓

Insulin, IGF-II ↔ ↑

TFG-β1 ↓ ↑

Question 14

Myostatin

Answer 14

• ↑ → ↑myoblast differentiation → ↓muscle size
• ↓ → ↑myoblast prolif → ↑muscle size

Question 15

Regulation: MicroRNA

Answer 15

• Small non-coding RNA
• Regulated by MRFs
• MyomiR = muscle specific miRNA
• miR - 1 & 206 → ↑ myoblast differentiation
  
  • Inhibits follistatin → inhibits myostatin
• miR - 133 → ↑ myoblast proliferation
  
  • Inhibits SRF → ↑proliferation