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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
Q

For an embryonic stem cells to become a muscle progenitor cell which two key genes must be turned on and expressed?

A

Pax7+

Pax3+

26
Q

What is additionally expressed in myoblasts?

A

MyoD+

In addition to:
Pax7+
Pax3+

27
Q

What are the changes in gene expression from a Myoblast to a Myotube?

A

Pax genes need to be downregulated

These genes are upregulated:
Myogenin +
SRF +
MyoD

28
Q

What are the specialised proteins for the maturation to the Myofibre from Myotubes?

A

MHC+ve

Myogenin+

29
Q

Factors controlling expression of Pax3/Pax7 are very complex but involve:

A 
Sonic hedgehog
Wnts
Notch
noggin
BMP4 - particularly
30
Q

Pax3 and Pax7 are highly homologous genes but only have overlapping fucntions during ____ ______-

A

myogenic specification

31
Q

True or false

Forced expression of either Pax3 or Pax7 can make an embryonic stem cell commit to becoming a muscle precursor cell

A

True

32
Q

What does loss of Pax3 only result in?

A

absense of limb muscles

33
Q

What does loss of Pax7 only result in?

A

Results in normal embryonic myogenesis but lack of adult ‘satellite cells

34
Q

What does loss of Pax7 and Pax3 result in?

A

complete absense of musculature

35
Q

Expression of Pax3 and Pax7 is essential for the regulation of ____ expression

A

Myogenic regulatory factors (MRF)

36
Q

Myogenic regulatory factors (MRF) are a family of very powerful transcription factors

All are similarly structured

what are the MRFs to remember?

A

MyoD, Myf5, Myogenin, MRF4

37
Q

Myogenic regulatory factors (MRF) are a family of very powerful transcription factors

All are similarly structured

what are the MRFs to remember?

A

Primary: MyoD, Myf5,

Myogenin, MRF4

38
Q

Primary and secondary RMFs having different roles in..

A

myogenesis

39
Q

MyoD, Myf5 are expresssed ___in muscle development

What is their key role?

A

MyoD, Myf5 are expresssed early in muscle development

promote expression of Myogenin and beginning of differentiaton

40
Q

What happens when either MyoD or Myf5 are knocked out?

A

muscles develop fine

They have redundancy with each other

41
Q

What happens wgen MyoD and Myf5 are both knocked out?

A

no skeletal muscle

42
Q

true or false

The secondary MRFs are reduntant to each other

A

False

Knockout either Myogenin and MRF4 and myoblast differentiation is severely affected

43
Q

What does Myogenin and MRF4 do?

A

promote expression of muscle-specific genes

e.g Myosin heavy chains

44
Q

What are the transcription factors that are key to myogenesis but aren’t MRFs?

A

MEF2 and SRF

45
Q

True or False

MEF2 and SRF can’t initiate myogenesis on their own but contribute to differentiation and maturation of muscle fibres

A

true

46
Q

What regulates the actual transcription factors during myogenesis?

A

Growth factors

Bind to cell surface receptors and induce cellular effects

Involve a variety of signalling cascade

47
Q

What are the two stages in which Growth Factors can affect both myogenesis and mature muscle?

A

Myogenesis: bu affecting proliferation and/or differentiation

Mature myofibres - by affecting protein metabolism
- Hyper trophy (muscle fibre growth) or atrophy (muscle fibre shrinking)

48
Q

What are the growth factors of interest?

A

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
Q

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
A

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
Q

Myostatin is traditionally recognised as an inhibitor of differentiation as inhibition of myostatin does what?

A

increases muscle mass

51
Q

Myostatin is an essential regulator of the balance between…

A

proliferation vs. differentiation of embryonic muscle progenitors

52
Q

Increased myostatin =

A

favoured myoblast differentiation = smaller muscles

53
Q

Decreased myostatin =

A

favoured myoblast proliferation = larger muscles

54
Q

Decreased myostatin =

A

favoured myoblast proliferation = larger muscles

55
Q

What are microRNA?

A

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
Q

myomiRs =

A

Muscle specific miRNAs

57
Q

miR-1/206 family enhances…

A

myoblast differentiation

58
Q

miR-133 family drives…

A

myoblast proliferation

59
Q

What is follistatin’s role?

A

antagonise myostation

60
Q

What effect will miR-1 and miR-206 have on follistatin?

A

inhibits follistatin

blocking the ‘‘blocker’’

61
Q

What does miR-133 inhibit?

A

SRF

blocking differentiation to favour proliferation

62
Q

From birth to adulthood muscle size increases ___ fold

A

20

But there is no significant change in muscle fibre number after birth

Muscle & Exercise Physiology (34 decks)

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