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Muscle & Exercise Physiology > Lecture 19 - Myogenesis: molecular bases of muscle development > Flashcards

Lecture 19 - Myogenesis: molecular bases of muscle development Flashcards

1
Q

Muscle cells are very ____ when compared to most other cells

A

large

up to 12 cm long

Each muscle fibre is a single muscle cell

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2
Q

Muscle cells are very ____ when comared to most other cells

A

large

up to 12 cm long

Each muscle fibre is a single muscle cell

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3
Q

Zygote –> ____–> _____

A

Zygote –> Blastula –> Gastrula –> Mesoderm

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4
Q

The mesoderm goes on to develop the ____ and ____

A

notochord and somites

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5
Q

Somites differentiate further to form the…

A

Myotome - from which our muscles arise

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6
Q

True or False

Early in embryo development, the mesoderm segments into somites

A

True

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7
Q

Where do somites form?

A

Somites are bilaterally paired blocks of mesoderm that form along the head to tail axis of a developing embryo

give rise to vertebrae, ribs, occipital bone, skeletal muscle, cartilage, tendons and skin

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8
Q

ALL skeltal muscle from the neck down is derived from ____

A

somites

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9
Q

Myoblasts migrate out from somite

What does the medial and laterla somite form?

A

Medial somite (near neural tube) forms the axial (trunk) muscles

Lateral somite (distal to neural tube) for the limb muscles

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10
Q

Some head and neck muscles are derived form the somite, such as the ____

A

tongue

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11
Q

True or False

The extra-ocular and jaw/facial muscles are derivied from somites

A

False

derived from the head mseoderm

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12
Q

A muscle cell is a syncytium, meaning..

A

A large mass of cytoplasm not separated into individual cells and contains many nuclei

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13
Q

A muscle cell is a syncytium, meaning..

A

A large mass of cytoplasm not separated into individual cells and contains many nuclei

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14
Q

Embryonic stem cell –> ____________—> ________—> _________—> mature myofibre

A

Embryonic stem cell –> Muscle progenitor cell —> Myoblast —> myotube —> mature myofibre

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15
Q

_______s exit the cell cycle, align and fuse together

A

Myoblasts

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16
Q

Myotubes recruit more myoblasts/nuclei and increase size to become ___ ______

A

Mature Myofibres

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17
Q

Myotubes recruit more myoblasts/nuclei and increase size to become ___ ______

A

Mature Myofibres

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18
Q

Muscle progenitor cells (MPCs) are what type of stem cell?

A

Multipotent

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19
Q

Myoblasts are committed to becoming muscle but do retain some characteristics of stem cells, including….

A

still being highly proliferative

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20
Q

What is the morphology of the myoblast?

A

Spindle shaped

Centrally nucleated

Highly proliferative

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21
Q

What is the morphology of the Myotube?

A

long structures

Terminally differentiated

Central nuclear chain (line up along the middle)

Can contract but lack specialised structures of muscle fibres

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22
Q

What happens to Myotubes to become mature myofibres?

A

Nuclei move the periphery

Specialised structures develop (e.g t-tubules, DGC becomes properly expressed and functional)

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23
Q

____ migrate to specific areas of the embryo where they proliferate

A

Myoblasts

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24
Q

Myogenesis is regulated by a complex network of …

A

Transcription factors

growth factors

microRNA (miRNA)

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25
For an embryonic stem cells to become a muscle progenitor cell which two key genes must be turned on and expressed?
Pax7+ Pax3+
26
What is additionally expressed in myoblasts?
MyoD+ In addition to: Pax7+ Pax3+
27
What are the changes in gene expression from a Myoblast to a Myotube?
Pax genes need to be downregulated | These genes are upregulated: Myogenin + SRF + MyoD
28
What are the specialised proteins for the maturation to the Myofibre from Myotubes?
MHC+ve | Myogenin+
29
Factors controlling expression of Pax3/Pax7 are very complex but involve:
``` Sonic hedgehog Wnts Notch noggin BMP4 - particularly ```
30
Pax3 and Pax7 are highly homologous genes but only have overlapping fucntions during ____ ______-
myogenic specification
31
True or false Forced expression of either Pax3 or Pax7 can make an embryonic stem cell commit to becoming a muscle precursor cell
True
32
What does loss of Pax3 only result in?
absense of limb muscles
33
What does loss of Pax7 only result in?
Results in normal embryonic myogenesis but lack of adult 'satellite cells
34
What does loss of Pax7 and Pax3 result in?
complete absense of musculature
35
Expression of Pax3 and Pax7 is essential for the regulation of ____ expression
Myogenic regulatory factors (MRF)
36
Myogenic regulatory factors (MRF) are a family of very powerful transcription factors All are similarly structured what are the MRFs to remember?
MyoD, Myf5, Myogenin, MRF4
37
Myogenic regulatory factors (MRF) are a family of very powerful transcription factors All are similarly structured what are the MRFs to remember?
Primary: MyoD, Myf5, Myogenin, MRF4
38
Primary and secondary RMFs having different roles in..
myogenesis
39
MyoD, Myf5 are expresssed ___in muscle development What is their key role?
MyoD, Myf5 are expresssed early in muscle development promote expression of Myogenin and beginning of differentiaton
40
What happens when either MyoD or Myf5 are knocked out?
muscles develop fine They have redundancy with each other
41
What happens wgen MyoD and Myf5 are both knocked out?
no skeletal muscle
42
true or false The secondary MRFs are reduntant to each other
False Knockout either Myogenin and MRF4 and myoblast differentiation is severely affected
43
What does Myogenin and MRF4 do?
promote expression of muscle-specific genes e.g Myosin heavy chains
44
What are the transcription factors that are key to myogenesis but aren't MRFs?
MEF2 and SRF
45
True or False MEF2 and SRF can't initiate myogenesis on their own but contribute to differentiation and maturation of muscle fibres
true
46
What regulates the actual transcription factors during myogenesis?
Growth factors Bind to cell surface receptors and induce cellular effects Involve a variety of signalling cascade
47
What are the two stages in which Growth Factors can affect both myogenesis and mature muscle?
Myogenesis: bu affecting proliferation and/or differentiation Mature myofibres - by affecting protein metabolism - Hyper trophy (muscle fibre growth) or atrophy (muscle fibre shrinking)
48
What are the growth factors of interest?
Insulin, IGF-1, IGF-2, HGF, FGF IL-6, IL-15, LIF TGF-beta family Can have positive or negative effects depending on what they're acting on
49
What is the effect on proliferation and differentiation for each of these growth factors ``` IGF-1 LLIF, IL-6 FGF, HGF Insulin, IGF-2 TGF-B1 ```
IGF-1 - increase proliferation, increase differentiation LLIF, IL-6 - increase proliferation, FGF, HGF - increase proliferation, decrease differentiation Insulin, IGF-2- increase differentiation TGF-B1 - decrease proliferation, increase differentiation
50
Myostatin is traditionally recognised as an inhibitor of differentiation as inhibition of myostatin does what?
increases muscle mass
51
Myostatin is an essential regulator of the balance between...
proliferation vs. differentiation of embryonic muscle progenitors
52
Increased myostatin =
favoured myoblast differentiation = smaller muscles
53
Decreased myostatin =
favoured myoblast proliferation = larger muscles
54
Decreased myostatin =
favoured myoblast proliferation = larger muscles
55
What are microRNA?
Small, non-coding RNAs that play a major role in cell development and differentiation by negatively regulating gene function several miRNAs have been shown to be reguolated by MRFs
56
myomiRs =
Muscle specific miRNAs
57
miR-1/206 family enhances...
myoblast differentiation
58
miR-133 family drives...
myoblast proliferation
59
What is follistatin's role?
antagonise myostation
60
What effect will miR-1 and miR-206 have on follistatin?
inhibits follistatin blocking the ''blocker''
61
What does miR-133 inhibit?
SRF blocking differentiation to favour proliferation
62
From birth to adulthood muscle size increases ___ fold
20 But there is no significant change in muscle fibre number after birth

Muscle & Exercise Physiology (34 decks)

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