Regeneration and Formation of Skeletal Muscle Flashcards
What is a somite?
blocks of cells formed from mesodermal cells adjacent to the neural tube.
How do skeletal muscle fibres form?
By fusion of myoblasts
Outline the steps of skeletal muscle fibre formation.
- Cells originating from the somites become determined as myoblasts (precursors of skeletal muscle fibers).’
- Myoblast differentiation
- As they differentiate, they fuse with one another to form multinucleated skeletal muscle fibers. Fusion involves specific cell-cell adhesion molecules that mediate recognition between newly differentiating myoblasts and fibers.
What does the commitment of the myoblasts depend on?
gene regulatory proteins of at least two families—the MyoD family of basic helix-loop-helix proteins, and the MEF2 family of MADS box proteins.
These act in combination to give the myoblast a memory of its committed state, and, eventually, to regulate the expression of other genes that give the mature muscle cell its specialized character.
What is myoblast differentiation?
After a period of proliferation, the myoblasts undergo a dramatic switch of phenotype that depends on the coordinated activation of a whole battery of muscle-specific genes
Once differentiation has occurred, do the cells divide?
No, they do not and the nuclei never replicate their DNA again
What can keep myoblasts proliferating, while they retain their ability to fuse to form muscle cells?
signal proteins such as fibroblast or hepatocyte growth factor
What happens when you culture myoblasts in culture without HGF and FGF?
The cells rapidly stop dividing, differentiate, and fuse.
What is another factor important to myoblast differentiation?
attachment to the extracellular matrix
How do skeletal muscle fibres modulate their properties according to their functional requirements?
By changing the protein isoforms they contain
When are the adult number of muscle fibres attained
Before birth
How long do skeletal muscles survive?
A lifetime
How is the postnatal increase in muscle bulk attained?
Cell enlargement as individual muscle nuclei are added.
How does growth in muscle length occur?
recruitment of more myoblasts into the existing multinucleated fibers, which increases the number of nuclei in each cell.
How does growth in muscle girth occur?
involves both myoblast recruitment and an increase in the size and numbers of the contractile myofibrils that each muscle fiber nucleus supports.
What is a mechanism that controls muscle cell number and size?
Extracellular signal protein - myostatin
What happens to myostatin loss-of-function mice?
have enormous muscles—two to three times larger than normal. Both the numbers and the size of the muscle cells seem to be increased.
What other animal has an myostatin related mutation?
Belgian Blue cattle lack myostatin and thus have giant muscles “double-muscled”
What is myostatin and where is it made?
Myostatin belongs to the TGFβ superfamily of signal proteins
It is normally made and secreted by skeletal muscle cells.
An autocrine/paracrine inhibitor of skeletal muscle growth
What is the function of myostatin?
to provide negative feedback to limit muscle growth.
myostatin may act as a negative regulator of muscle growth in adult life as well as during development.
It inhibits proliferation, differentiation and enhances degradation
What is the muscle structure hierarchy?
Myofilaments –> myofibril –> myofiber/myotube (aka. muscle fiber) –> fascicle –> muscle
Define a satellite cell
a stem cell that lies adjacent to a skeletal muscle fiber and plays a role in muscle growth, repair, and regeneration.
Where are the satellite cells?
They are retained as small, flattened, and inactive cells lying in close contact with the mature muscle cell and contained within its sheath of basal lamina.
What happens when muscle is damaged/ must repair after exercise?
satellite cells are activated to proliferate, and their progeny can fuse to repair the damaged muscle.
Where does most muscle tissue in the body come from?
embryonic mesoderm
How are muscle cells in the head and limbs different from other skeletal muscle cells?
They originate from the general mesoderm not the mesodermal somites
What is a myoblast?
muscle-forming stem cell that migrates to different regions in the body and then fuse(s) to form a syncytium, or myotube.
How do neuromuscular junctions form along muscle cells?
In skeletal muscles, ACh receptors are initially present along most of the surface of the myoblasts, but spinal nerve innervation causes the release of growth factors that stimulate the formation of motor end-plates and NMJs.
How limited are the regenerative capabilities of satellite cells?
Satellite cells can regenerate muscle fibers to a very limited extent, but they primarily help to repair damage in living cells.
What happens if a cell is damaged to a greater extent than satellite cells can regenerate?
the muscle fibers are replaced by scar tissue in a process called fibrosis.
Scar tissue cannot contracts and muscle that has sustained significant damage cannot produce the same amount of power or endurance.
What might increase the mass and bulk of skeletal muscle?
hormones and stress (and artificial anabolic steroids)
What might decrease skeletal muscle bulk and mass?
Disuse (due to being in a cast or paralysis due to eg. Polio), age
What regulates the proliferation and fusion of satellite cells?
A group of basic helix loop helix transcription factors
List the main four myogenic regulatory factors
MyoD, Myf5. MRF4, Myogenin
Which regulatory factors are involved in satellite cell proliferation?
MyoD and Myf5
Which regulatory factors are involved in fusion of committed myogenic precursor cells into the myofibre for repair?
MRF4 and Myogenin