Lecture 7 - Muscle

Question 1

what is a sarcoemere

Answer 1

the structural unit of a myofibril in a striated muscle

Question 2

wgat us the smallest cellular unit of a muscle and it’s mportant property

Answer 2

myofibre

polynucleated

Question 3

what do myofibres consist of

Answer 3

many myofibrils

Question 4

how are somites patterned

Answer 4

siganals from adjacent tissues including notochord and lpm ectoderm etc
distinct code
distinct TF
give identity

Question 5

with the following signals what tissues release the signals
-WNts 
Shh
noggin
Bmp

Answer 5

Wnts = from the dorsal n.tube and epidermal ectoderm
Bmp4 lateral plate
Shh (and noggin) = notochord and floor plate of n.tubw

Question 6

What do the signals define?
wnt
shh
bmp

Answer 6

wnt - induce Pax3 expr defines dermomyotome and supreses sclerotome form
shh- induce pax1 - sclerotome
bmp4 controls sim1 ecpr in the lateral/hypaxial

Question 7

where do muscles form from

Answer 7

somites

competence at compartmentalisation

Question 8

what the different TF combine to give identity to diff compartments of the somite

Answer 8

dorsal 
Pax3/Pax7/En1 = epaxial muscles
pax3/pax7/sim1=hypaxial   = muscles
VEntral
sim1=hypaxial - sclerotome
pax1 - epaxial - sclerotome

Question 9

what compartment are muscle precursors in somite

Answer 9

hypaxial - dorsal

bmp and wnt cooperate to specify

Question 10

what is the dermomytome

Answer 10

pool of precursors cells of muscles

Question 11

what is the sclerotome and how does it form

Answer 11

EMT (deepithalises) leaves behind dermomyotome and the myotome
gives rise to themcartilage and bone of the axial skeleton and ribs

Question 12

what are the different sections of myotome

Answer 12

dorsomedial lip
dermomytome proper
early myotome
ventrolateral lip

Question 13

descirbe propetries of the myotome

Answer 13

forms in rib musculature

first differnetiated muscle cell

Question 14

what happens to Tf patterns from the tranistion form somites to dermomytome

Answer 14

are maintained
pax3/pax7 = muscle precursors
my15 - onset of differnetiation in myotome and lips

Question 15

how is progenitor migration steered

Answer 15

signals from limb to receotive muscle precursors (which are in the ventrolateral lip )

Question 16

what are the signals thta guide the cell migration and where are they expressed

Answer 16

siganl =SDF1 rec = CXCR4
expr where pax3 upreg - in limb region where limb will form
signal SF/HGF rec Cmet/hgf

Question 17

what happens to the cells that get the singal and become migratory

Answer 17

emt (epithelial mesodermal transition)

Question 18

what is epithelial mesodermal tranisiton

Answer 18

cells give up epithelial identitiy and become migratory

Question 19

what tf define the expression of the signals SF/HGF

Answer 19

Fgf4/8 from the aer

Question 20

how do fgf4/8 from aer indirectly effect SDF1 signal

Answer 20

fgf impct on Lbx1 exor
lbx1 control cxcr4 expression
= why only cxcr4 in prospective limb

Question 21

what do teh Sf/cMEt mutants show

Answer 21

that with no rec there is no migration but the muscle precursor cells (lbx1 positive) accumulate in areas where is signal

Question 22

what do SDF-CXCR4 mutatns show

Answer 22

implant of sdf1 attract cxcr4 positive cells
- ectopic muscle
control implant no effect

Question 23

what the fucntional relationship between C-met and cxcr4

Answer 23

partially reduncant

strong ptype only when both taken out

Question 24

from studies in sebrafish what tf has been implicated in the formatino of multinucleate myotubes

Answer 24

kirrel

Question 25

what is the tf that define the myoblast (taking over from pax expr)

Answer 25

Myod Myf5 Desmin

Question 26

what cells are likely to contribute to the induction of Myf5 expression

Answer 26

neural crest cells

Question 27

how are ncc cells thought to induce Myf5

Answer 27

neural crest cells express delta =activate notch signalling notch switches on myf5

Question 28

what transcription facotrs are key determinants of muslce differentiation

Answer 28

``` myf5 mrf4 myoD myogenin = all members of MDF/MRF family ```

Question 29

what is the expression patterns of the MDF/MRF family

Answer 29

=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

Question 30

what MRF fam member is suff and req for myogenic fate in culture

Answer 30

myod (ko and rescue) when ko myod act myf5 but no other myogenic factors - suggets myod the inductive signal

Question 31

what results show there is a high degree of interdepndence in teh myogenic factors

Answer 31

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

Question 32

what is mef2

Answer 32

master reg of muscle differntiation | downstream of the MDF/MRF

Question 33

what do mef2 mut show

Answer 33

early stages of precurso and specification -normal specific differentiation -normal functional differneitation doesnt occur (mef2 act genes form myocyte fusion/anchor/innervation)

Question 34

what factors does mef2 activate

Answer 34

mbc | integrin

Question 35

what ptype for lof mbc and integrin

Answer 35

mbc -no fusion (mono - poly) but differentiate | integrin - fail to attach properly /not proper cell junction

Question 36

what mechnaism is used to maintain progenitors

Answer 36

asym div

Question 37

what is the role of notch in asym div

Answer 37

precursors expr notch - beroe div switch on numb = decr notch - allows MDF expr as norm notch singal via RBP-j inh mdf

Question 38

what is the pheontype of delta dbl mut mouse | rbpj mut

Answer 38

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

Question 39

what are satelite cells ?

Answer 39

muscle precursor cell remian undiff in adult | expr PAX7 and notch

Question 40

how was the regenerative power of satelite cells shown

Answer 40

conditional ko of in differnentiated uscle fibres causes hyperttrophy - satelite cells not effected get over induced to regerate muscle

Question 41

What strucutures does the sclerotome give rise to?

Answer 41

bones of the vertebra and ribs

Question 42

what structures does the dermomyotome give rise to

Answer 42

dermis and skeletal muscle