striated muscle monique berendse & catriona · pdf filemrfs = skeletal muscle specific hlh...

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