Lecture 18 Flashcards
What is myogenesis?
Myogenesis is the synthesis of new muscle.
What process forms the 3 germ layers during embryogenesis? What are these 3 layers?
3 germ layers formed by gastrulation; ectoderm, endoderm, and the mesoderm.
What does the mesoderm form?
Mesoderm forms the notochord and somites
What do somites form?
somites form myotome sclerotome and dermatome.
What part of the somite forms muscles?
myotome forms muscles
What muscles are formed from somites?
All muscles from the neck down are formed from somites plus the tongue.
What structures do somites give rise to?
Vertebrae + ribs + occipital bone
Skeletal muscle (from the neck down)
Cartilage, Tendons
Skin
What are the 2 type of somites and what muscles do they form?
Medial somite forms the axial muscles.
Lateral somites form limb muscles
What structures do myoblasts form from during embryogenesis? (structures not cells)
myoblasts form from medial and lateral somites and form muscles.
What is a syncytium?
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.
How do myotubes form myofibers?
From myotube to myoblast requires fusion of more myoblasts.
Why are muscle progenitor cells said to be multipotent and not totipotent?
Muscle progenitor cell is multipotent because they are stem cells that can’t form absolutely everything.
What are some stem cell properties of myoblasts?
Highly proliferative
Can differentiate rapidly
It can renew itself
What are features of the myoblast?
Highly proliferative
Spindle shaped
Centrally nucleated
What are features of myotubes?
Terminally differentiated (cannot proliferate anymore)
Lots of nuclei.
What is the difference between myotubes and myofibers?
Myotubes are centrally nucleated whereas mature myofibers move nuclei to the periphery.
Myotubes can contract but lack the specialized structures of myofibers.
What are the regulatory mechanisms of embryogenic myogenesis?
Transcription factors
Growth factors
MicroRNA
What does an embryonic stem cell require to become a muscle progenitor cell?
Pax3+
Pax7+
What genes are expressedin myoblasts that aren’t expressed in muscle progenitor cells?
myoD+
What genes are expressed during differentiation into myotubes?
Pax7+ and Pax3+ are down regulated
Moyogenin and SRF are upregulated
What genes are expressed during myofiber formation?
To form a myofiber upregulation of myogenin+ and MHC+ve are upregulated.
What is the chemical messenger required to turn an embryonic stem cell into a muscle progenitor cell?
BMP
What are the factors controlling expression of Pax3 and Pax7?
Sonic Hedgehog
Wnts
Notch
Nogin
BMP4
What Pax genes do cells of embryonic muscles typically express during embryogenesis?
Cells express either Pax3 or Pax7 or both.
How do Pax3 and Pax7 work together during embryogenesis?
Pax3 and Pax7 are highly homologous genes. They have overlapping functions during myogenic specification.
What happens if Pax3 and Pax 7 are both lost?
No muscle production.
What happens if no Pax3 is expressed?
Limb muscles are not developed.
What happens if no Pax7 is expressed?
Normal embryogenesis but no satellite cell formation.
What 2 genes need to be expressed for MRF expression?
Pax7
Pax3
What is the function of MRFs?
MRFs are expressed in muscle progenitor cells to form the differentiation into myoblasts and myotubes
What are the MRFs involved in muscle differentiation?
MyoD
Myf5
Myogenin
MRF4
How powerful are MRFs?
They can turn fat or fibrotic tissue into muscle.
What is the structure of MRF proteins like?
MRF proteins are a family of proteins with a helix - loop - helix structure needed to bind DNA.
What are the 2 subdivisions of MRF proteins? What is the difference in their functions? What are examples of each?
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)
What are the non MRF transcription factors important for myogenesis?
MEF2 and SRF are not MRFs but are important transcription factors for differentiation to occur.
What are growth factors?
Growth factors bind to cell surface receptors and induce cellular effects and involve signal cascades.
How do growth factors affect myogenesis?
Myogenesis affects proliferation and differentiation of myoblasts and myotubes.
How do growth factors affect mature fibers?
Mature myofibers growth factors affect hypertrophy and protein metabolism.
What growth factors increase both proliferation and differentiation?
IGF-1
Which growth factors increase proliferation without affecting differentiation?
LIF
IL-6
Which growth factors increase proliferation and decrease differentiation?
FGF
HGF
Which growth factors increase differentiation without affecting proliferation?
Insulin
IGF-2
Which growth factors decrease proliferation and increase differentiation?
TGF-Beta1 (aka myostatin)
What is the difference between differentiation and proliferation?
increased myoblast differentiation means more myotube formation but less myoblasts which leads to
What is the function of follistatin and how do miRNAs influence its function and in turn myostatin’s function?
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.
What is the function of miR-1 and miR-206?
Inhibit the inhibitor of myostatin which results in myostatin expression.
What is the result of over-expression of follistatin?
over-expression of follistatin results in more proliferation and these muscles differentiate by other factors this is a result of myostatin inhibition.
What happens to muscle fiber number during muscle growth?
from birth to adulthood no new muscle fibers are produced but rather the size of each muscle fibers grow individually.
What is the function of miR-133?
To inhibit differentiation and promote further proliferation of myoblasts
