• How do skeletal muscles develop?

• • All multicellular organisms start as one cell

• • Embryogenesis: The processes leading to the

• development of an embryo from an egg

Diagram of a cross-section through an early vertebrate embryo

Germ layers : the 3 layers of cells comprising the early embryo

Diagram of a cross-section through an early vertebrate embryo

Somite : segmentally arranged blocks of mesoderm

HOW DO MUSCLE FIBERS DEVELOP IN THE BODY?A : Mesodermal

cell

- undifferentiated

-“presumptive

myoblast” or

“muscle precursor

cell”

-proliferative

(mitotic)

HOW DO MUSCLE FIBERS DEVELOP IN THE BODY?

B : Myoblast

- spindle-shaped

- microtubules and

filaments

- ribosomes

HOW DO MUSCLE FIBERS DEVELOP IN THE BODY?

C : Myotube

- myoblasts fuse

- multinucleated

- myofibrils

- immature fiber

- non-mitotic

HOW DO MUSCLE FIBERS DEVELOP IN THE BODY?

A : Mesodermal

cell

B : myoblast

C : myotube

D : fiber

-sarcomeres

-peripheral nuclei

WHAT CONTROLS THESE STEPS?

Myogenic differentiation pathway involves:

(1) Determination of mesodermal precursors as myoblasts,

(2) Differentiation of myoblasts into multinucleated myotubes, and

(3) Maturation of myotubes into fibers is completed by innervation

Myogenic Regulatory Factors (MRFs)

• MRFs

--Transcription factors : nuclear proteins that bind DNA

– All contain a basic helix-loop-helix (sequence homology)

– Bind to E-box sequence at 5’ end of many muscle genes

(desmin, myosin light chain, troponin, creatine kinase, etc)

• MyoD Family

• E-proteins

• Myocyte enhancer factors (MEFs)

• Inhibition of differentiation (Id) factors

HOW DO SKELETAL MUSCLES GROW?• Hypertrophy

– Increase in fiber diameter (and/or fiber length)

– Primary method for muscles to increase in size

• Hyperplasia

– Increase in number of fibers

– Occurs to a very limited extent

– Basically, the number of muscle fibers at birth

does not increase

• Hormones

– Growth Hormone (Somatotropin)

– Testosterone

– Insulin

– Estrogens

“Anabolic steroids” work primarily by increasing

protein accretion

• Hormones

• Growth Factors

– Includes cytokines and hormones

– Produced locally in differentiated muscle (influenced by

hormones) and external to muscle

– Regulate proliferation, differentiation, and growth (+, -)

in muscle

• IGF

• FGF

• HGF

• TGF-ß (myostatin aka GDF-8)

• Passive Stretch*

• Work (Exercise)* • Nutrition

MAIN EVENTS LEADING TO MUSCLE GROWTH