Lecture 18 Flashcards

1
Q

What is myogenesis?

A

Myogenesis is the synthesis of new muscle.

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2
Q

What process forms the 3 germ layers during embryogenesis? What are these 3 layers?

A

3 germ layers formed by gastrulation; ectoderm, endoderm, and the mesoderm.

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3
Q

What does the mesoderm form?

A

Mesoderm forms the notochord and somites

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4
Q

What do somites form?

A

somites form myotome sclerotome and dermatome.

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5
Q

What part of the somite forms muscles?

A

myotome forms muscles

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6
Q

What muscles are formed from somites?

A

All muscles from the neck down are formed from somites plus the tongue.

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7
Q

What structures do somites give rise to?

A

Vertebrae + ribs + occipital bone

Skeletal muscle (from the neck down)

Cartilage, Tendons

Skin

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8
Q

What are the 2 type of somites and what muscles do they form?

A

Medial somite forms the axial muscles.

Lateral somites form limb muscles

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9
Q

What structures do myoblasts form from during embryogenesis? (structures not cells)

A

myoblasts form from medial and lateral somites and form muscles.

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10
Q

What is a syncytium?

A

A syncytium refers to a cell with a large muscle cytoplasm not separated into individual cells. It is formed by fusion of many cells and has many nuclei.

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11
Q

How do myotubes form myofibers?

A

From myotube to myoblast requires fusion of more myoblasts.

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12
Q

Why are muscle progenitor cells said to be multipotent and not totipotent?

A

Muscle progenitor cell is multipotent because they are stem cells that can’t form absolutely everything.

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13
Q

What are some stem cell properties of myoblasts?

A

Highly proliferative

Can differentiate rapidly

It can renew itself

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14
Q

What are features of the myoblast?

A

Highly proliferative

Spindle shaped

Centrally nucleated

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15
Q

What are features of myotubes?

A

Terminally differentiated (cannot proliferate anymore)

Lots of nuclei.

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16
Q

What is the difference between myotubes and myofibers?

A

Myotubes are centrally nucleated whereas mature myofibers move nuclei to the periphery.

Myotubes can contract but lack the specialized structures of myofibers.

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17
Q

What are the regulatory mechanisms of embryogenic myogenesis?

A

Transcription factors

Growth factors

MicroRNA

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18
Q

What does an embryonic stem cell require to become a muscle progenitor cell?

A

Pax3+

Pax7+

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19
Q

What genes are expressedin myoblasts that aren’t expressed in muscle progenitor cells?

A

myoD+

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20
Q

What genes are expressed during differentiation into myotubes?

A

Pax7+ and Pax3+ are down regulated

Moyogenin and SRF are upregulated

21
Q

What genes are expressed during myofiber formation?

A

To form a myofiber upregulation of myogenin+ and MHC+ve are upregulated.

22
Q

What is the chemical messenger required to turn an embryonic stem cell into a muscle progenitor cell?

A

BMP

23
Q

What are the factors controlling expression of Pax3 and Pax7?

A

Sonic Hedgehog

Wnts

Notch

Nogin

BMP4

24
Q

What Pax genes do cells of embryonic muscles typically express during embryogenesis?

A

Cells express either Pax3 or Pax7 or both.

25
Q

How do Pax3 and Pax7 work together during embryogenesis?

A

Pax3 and Pax7 are highly homologous genes. They have overlapping functions during myogenic specification.

26
Q

What happens if Pax3 and Pax 7 are both lost?

A

No muscle production.

27
Q

What happens if no Pax3 is expressed?

A

Limb muscles are not developed.

28
Q

What happens if no Pax7 is expressed?

A

Normal embryogenesis but no satellite cell formation.

29
Q

What 2 genes need to be expressed for MRF expression?

A

Pax7

Pax3

30
Q

What is the function of MRFs?

A

MRFs are expressed in muscle progenitor cells to form the differentiation into myoblasts and myotubes

31
Q

What are the MRFs involved in muscle differentiation?

A

MyoD

Myf5

Myogenin

MRF4

32
Q

How powerful are MRFs?

A

They can turn fat or fibrotic tissue into muscle.

33
Q

What is the structure of MRF proteins like?

A

MRF proteins are a family of proteins with a helix - loop - helix structure needed to bind DNA.

34
Q

What are the 2 subdivisions of MRF proteins? What is the difference in their functions? What are examples of each?

A

MRF proteins can be subdivided into primary and secondary MRFs; Primary MRFs include: MyoD and Myf5 which are produced early in development. If one is knocked out muscles develop fine but if both don’t work no skeletal muscle develops.

Secondary MRFs; Myogenin & MRF4 are expressed later during differentiation and promote further differentiation & specialization. Secondary MRFs don’t have redundancy. These MRFs promote expression of muscle specific genes. (eg. MyHC)

35
Q

What are the non MRF transcription factors important for myogenesis?

A

MEF2 and SRF are not MRFs but are important transcription factors for differentiation to occur.

36
Q

What are growth factors?

A

Growth factors bind to cell surface receptors and induce cellular effects and involve signal cascades.

37
Q

How do growth factors affect myogenesis?

A

Myogenesis affects proliferation and differentiation of myoblasts and myotubes.

38
Q

How do growth factors affect mature fibers?

A

Mature myofibers growth factors affect hypertrophy and protein metabolism.

39
Q

What growth factors increase both proliferation and differentiation?

A

IGF-1

40
Q

Which growth factors increase proliferation without affecting differentiation?

A

LIF

IL-6

41
Q

Which growth factors increase proliferation and decrease differentiation?

A

FGF

HGF

42
Q

Which growth factors increase differentiation without affecting proliferation?

A

Insulin

IGF-2

43
Q

Which growth factors decrease proliferation and increase differentiation?

A

TGF-Beta1 (aka myostatin)

44
Q

What is the difference between differentiation and proliferation?

A

increased myoblast differentiation means more myotube formation but less myoblasts which leads to

45
Q

What is the function of follistatin and how do miRNAs influence its function and in turn myostatin’s function?

A

Follistatin typically inhibits myostatin function and mir-1 and 206 drives myostatin differentiation whereas mir-133 inhibits differentiation and as a result leads to proliferation of myoblast.

46
Q

What is the function of miR-1 and miR-206?

A

Inhibit the inhibitor of myostatin which results in myostatin expression.

47
Q

What is the result of over-expression of follistatin?

A

over-expression of follistatin results in more proliferation and these muscles differentiate by other factors this is a result of myostatin inhibition.

48
Q

What happens to muscle fiber number during muscle growth?

A

from birth to adulthood no new muscle fibers are produced but rather the size of each muscle fibers grow individually.

49
Q

What is the function of miR-133?

A

To inhibit differentiation and promote further proliferation of myoblasts