striated muscle monique berendse & catriona · pdf filemrfs = skeletal muscle specific hlh...
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Striated muscleMonique Berendse & Catriona Lloyd
STRUCTURE AND FUNCTION
Vesicles with neurotransmitter
Synaptic Cleft
Presynaptic membrane
Postsynaptic membrane
Brain
Spinal Cord
Cross Section of Spinal Cord
Motor neuronecell body
Motor neurone axon
Muscle fibres
Neuromuscular Junction (NMJ) or Synapse
Details of NMJ
Muscle fibre
Nerve
Shalakadze, Grounds (2003). Therapeutic interventions for age-related muscle wasting: importance of innervationand exercise for preventing sarcopeniaBiology of Ageing and its modulationKluwer, Netherlands. 5: Chapter X
Structure of Skeletal Muscle
Sarcolemma
Nucleus
Mitochondria
Myofibrils
T-tubule
Sarcoplasmicreticulum
Terminal Cisternae
Thea Shavlakadze
skeletal muscle formation
Skeletal muscle is formed in somites
Various kinds of embryonic muscle
Waves of muscle formation
fast slow
Some major genes involved in muscle formationduring embryogenesis.
• Sonic hedgehog (day E8.5 in mouse) • Wnts (Wnt1–Myf5; Wnt7-MyoD)• Pax (Pax3-early; Pax7-later + satellite cells)MRFs = Skeletal muscle specific HLH transcription factors
Note: these are NOT expressed in cardiac muscle, despite very similar sarcomere structure.
• Myf5-early in myoblasts• MyoD-early in myoblasts• Myogenin-later during differentiation and in myotubes• MRF4-in mature muscleSarcomere proteins: isoforms of actin, myosin, tropomyosin
Multiple Functions → Alternate splicing of Pax7 RNA generates multiple isoforms
Pax7DPax7CPax7BPax7A
Hexanucleotide(CTTTAG)
Trinucleotide(CAG)
Transcript
5` 3`Exon 2 Exon 3 Exon 4
Encode paired domain
Exon 2 Exon 3 Exon 4
tri hexGene (antisense) / full length RNA
Spliced mRNA → 4 transcripts (cDNA)
Protein → 4 isoforms
CTTTAGCAG
G-LQ
DNA
[Chi and Epstein, 2002]
Some major genes involved in muscle formationduring embryogenesis.
• Sonic hedgehog (day E8.5) • Wnts (Wnt1–Myf5; Wnt7-MyoD)• Pax (Pax3-early; Pax 7 -later +satellite cells)MRFs = Skeletal muscle specific HLH transcription factors
Note: these are NOT expressed in cardiac muscle, despite very similar sarcomere structure.
• Myf5-early in myoblasts• MyoD-early in myoblasts• Myogenin-later during differentiation and in myotubes• MRF4-in mature muscleSarcomere proteins: isoforms of actin, myosin, tropomyosin
Skeletal muscle formationSkeletal muscle formation
MyoblastsMyoblasts MyotubeMyotube MyofibreMyofibre(only part is shown)(only part is shown)
Interstitial Interstitial connective tissueconnective tissue
Satellite cellSatellite cell Muscle nucleiMuscle nuclei
Basement membraneBasement membrane
Myogenic Stem Cellsand Regeneration
Satellite cellTerry Partridge
myotubesmyofibre(only part is shown)
myoblasts
1 satellite cell3 myonucleus
2 multipotential/stem cell
Sources of myoblasts within skeletal muscle
Myoblast or Multipotential/Stem Cell
Myonucleus
Membrane
Damaged Myofibre
myotubesmyofibre(only part is shown)
myoblasts
1 satellite cell3 myonucleus
2 multipotential/stem cell
Sources of myoblasts within skeletal muscle
Plasticity of STEM cells
Resident C/T cellsResident C/T cells skeletal cardiacpluripotent STEM cells (multi)progenitor cells
Vascular Vascular (mesangioblasts)endothelialsmooth muscle ( )pericytes ?
MyofibroblastsMyofibroblasts ( )EctopicEctopic cells cells (chickens)(chickens)Thymus Thymus (myoid cells)NeuralNeural ((multimulti)) ( ) DermisDermisCirculating boneCirculating bone--marrow marrow **((multimulti)) **
Stem cells and repair of muscle
Skeletal Cardiac
SarcomeresCatriona Lloyd & Monique Berendse