Lecture 7 - Muscle Flashcards
what is a sarcoemere
the structural unit of a myofibril in a striated muscle
wgat us the smallest cellular unit of a muscle and it’s mportant property
myofibre
polynucleated
what do myofibres consist of
many myofibrils
how are somites patterned
siganals from adjacent tissues including notochord and lpm ectoderm etc
distinct code
distinct TF
give identity
with the following signals what tissues release the signals -WNts Shh noggin Bmp
Wnts = from the dorsal n.tube and epidermal ectoderm
Bmp4 lateral plate
Shh (and noggin) = notochord and floor plate of n.tubw
What do the signals define?
wnt
shh
bmp
wnt - induce Pax3 expr defines dermomyotome and supreses sclerotome form
shh- induce pax1 - sclerotome
bmp4 controls sim1 ecpr in the lateral/hypaxial
where do muscles form from
somites
competence at compartmentalisation
what the different TF combine to give identity to diff compartments of the somite
dorsal Pax3/Pax7/En1 = epaxial muscles pax3/pax7/sim1=hypaxial = muscles VEntral sim1=hypaxial - sclerotome pax1 - epaxial - sclerotome
what compartment are muscle precursors in somite
hypaxial - dorsal
bmp and wnt cooperate to specify
what is the dermomytome
pool of precursors cells of muscles
what is the sclerotome and how does it form
EMT (deepithalises) leaves behind dermomyotome and the myotome
gives rise to themcartilage and bone of the axial skeleton and ribs
what are the different sections of myotome
dorsomedial lip
dermomytome proper
early myotome
ventrolateral lip
descirbe propetries of the myotome
forms in rib musculature
first differnetiated muscle cell
what happens to Tf patterns from the tranistion form somites to dermomytome
are maintained
pax3/pax7 = muscle precursors
my15 - onset of differnetiation in myotome and lips
how is progenitor migration steered
signals from limb to receotive muscle precursors (which are in the ventrolateral lip )
what are the signals thta guide the cell migration and where are they expressed
siganl =SDF1 rec = CXCR4
expr where pax3 upreg - in limb region where limb will form
signal SF/HGF rec Cmet/hgf
what happens to the cells that get the singal and become migratory
emt (epithelial mesodermal transition)
what is epithelial mesodermal tranisiton
cells give up epithelial identitiy and become migratory
what tf define the expression of the signals SF/HGF
Fgf4/8 from the aer
how do fgf4/8 from aer indirectly effect SDF1 signal
fgf impct on Lbx1 exor
lbx1 control cxcr4 expression
= why only cxcr4 in prospective limb
what do teh Sf/cMEt mutants show
that with no rec there is no migration but the muscle precursor cells (lbx1 positive) accumulate in areas where is signal
what do SDF-CXCR4 mutatns show
implant of sdf1 attract cxcr4 positive cells
- ectopic muscle
control implant no effect
what the fucntional relationship between C-met and cxcr4
partially reduncant
strong ptype only when both taken out
from studies in sebrafish what tf has been implicated in the formatino of multinucleate myotubes
kirrel
what is the tf that define the myoblast (taking over from pax expr)
Myod
Myf5
Desmin
what cells are likely to contribute to the induction of Myf5 expression
neural crest cells
how are ncc cells thought to induce Myf5
neural crest cells express delta
=activate notch signalling
notch switches on myf5
what transcription facotrs are key determinants of muslce differentiation
myf5 mrf4 myoD myogenin = all members of MDF/MRF family
what is the expression patterns of the MDF/MRF family
=myf5/mrf4/myod expr in undiff cells
myod - in venrtal lip
mrf4 / myf5 strong expr in myotome weak in ventral lip
myogenin expr duirng differentiation high in both myotome and ventral lip
what MRF fam member is suff and req for myogenic fate in culture
myod (ko and rescue)
when ko myod act myf5 but no other myogenic factors
- suggets myod the inductive signal
what results show there is a high degree of interdepndence in teh myogenic factors
1)l myf5/mrf4 redundancy, early myogensis depends on
2) limb specific myogensis req myf5 and myod only
3)myotome-derived body musculature is more dependent on redundant functions of myf5 and mrf4
= redundsancy but have time and spatial expr imp
what is mef2
master reg of muscle differntiation
downstream of the MDF/MRF
what do mef2 mut show
early stages of precurso and specification -normal
specific differentiation -normal
functional differneitation doesnt occur
(mef2 act genes form myocyte fusion/anchor/innervation)
what factors does mef2 activate
mbc
integrin
what ptype for lof mbc and integrin
mbc -no fusion (mono - poly) but differentiate
integrin - fail to attach properly /not proper cell junction
what mechnaism is used to maintain progenitors
asym div
what is the role of notch in asym div
precursors expr notch -
beroe div switch on numb = decr notch
- allows MDF expr as norm notch singal via RBP-j inh mdf
what is the pheontype of delta dbl mut mouse
rbpj mut
delta
precocious muscle differentiation and cessation of myogenesis
= using up of the muscle precursor pool
RBP-j
less undifferentiated myogenic cells at all stages of development
what are satelite cells ?
muscle precursor cell remian undiff in adult
expr PAX7 and notch
how was the regenerative power of satelite cells shown
conditional ko of in differnentiated uscle fibres causes hyperttrophy - satelite cells not effected get over induced to regerate muscle
What strucutures does the sclerotome give rise to?
bones of the vertebra and ribs
what structures does the dermomyotome give rise to
dermis and skeletal muscle
