skeletal muscle regeneration Flashcards
embryological origin of skeletal muscle
paaraxial mesoderm
origin of axial and limb skeletal muscles
para-axial mesoderm
origin of vertebrae, ribs, tendons
sclerotome
origin of bones and connective tissue in limbs
lateral plate mesoderm
EMT effectors
growth factors, cytokines and ECM
MET effects
adhesion, cortical actin,
EMT
cellular interaction with ECM
concentration gradients
MET
cell to cell interactions
wnt signalling pathway
wnt –> firzzled –> disheveled –I GSK-3 –I beta-catenin –> transcription
BMP signalling
need to dimeraise and bind protein - 2 receptors
FGF signalling
ligand based- activation of TFs
non-ligand based due to cell adhesion molecules
Myogenesis
- non-committed muscle prescursor cells
- drop in cell proliferation, drop in FGF and FGFr, drop in Id, rise in Pax7 - committed myoblasts
- myogenic TF induce skeletal muscle gene expression - immature myotube cell fusion
- myognenin is expressed - myotube
- developed muscle fibre, nuclei displaced under membrane
myogenic TFs and myogenesis
basic Helix-loop-helix TF
Myf-5, MyoD, MRF4, myogenin
repressors = Id (HLH) and ImF
Myogenic TF bind to E proteins; Id socks up E proteins to lower MTFs-E protein complexes
HLH region allows two TF to bind
BAsic region binds to DNA motif
repressors are almost like myogenic TF but have NO basic region
regulators bind to MyoD but because there is no basic region it can’t bind to DNA. therfeore concentration dependent
differentation of myoblast
induced by p21, p38 and Rb which prevents reentry into cell cycle
mature vs nonmatrue myoblast
immautre = myogenin positive mature = desmin positive
myoblast fusion to a myotube
myoblast allignment (cell-ECM) myoblast fusion (cell-cell adhesion followed by fision)
myoblast fusion
- fusion competent cell extend filopodia to myotube
- cell-cll recognition
- adhesion complexes
- plaue formation
- cell allignemnt and close apposition of plasma membrane
- membrane breakdown and fusion pore formation
- myotube
formation of adhesion plaque
expression on the cell surface of cell surface receptors
signalling pathway of mysin isotype expression (fast or slow)
tonic acctivity — slow motor neuron with small diamter. low calcium amplitude and long duration —> incrase in calcineurin —> dephosphorylation of NFAT
phasic activity —> fast motor neuron with large diameter
increased amplitude of calcium with short duration
phosphorylation of NFAT
motor nerve activity
required for primary myotubule and not secondary
satellite shape
round = satellite cell cigar = myogenic TF
myoD;myf5 ratio
myoD> myf5 - differentiation
myoD< Myf5 - proliferation and delyared differentation
pax 7 :myoD ratio
Pax7 > MyoD - quiescent
Pax7 = MyoD- proliferation but not differentiation
Pax7 < MyoD- differentiation with activation of myogenein
