Chapter 12 The molecular and cellular biology of skeletal muscle myogenesis: Practical applications

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Summary

Muscle fibers form during embryogenesis by the fusion of mononucleate myoblasts to form multinucleate syncytia. Myoblasts are determined somitic mesoderm cells that migrate to sites of myogenesis throughout the body in a biphasic fashion. Migration to the premuscle masses and the location of myoblasts on the extracellular matrix is controlled by a family of extracellular matrix receptors, the integrins. Fusion of growth-arrested myoblasts is controlled by two complementary adhesion systems—the Ca2+ dependent and Ca2+ independent systems. Progression of myoblasts through the various compartments of myogenesis is controlled by a family of muscle-specific proteins, the bHLH proteins. Following fusion, the newly formed myotubes follow a typical pattern of development based upon their lineage. Mature fibers retain the ability to change their physiological properties in response to environmental cues, which are responsible for building the adult characteristics of the different muscle groups. Postnatal growth occurs in response to a variety of stimuli by the fusion of myoblasts derived from satellite cells associated with adult fibers. In response to muscle damage caused by either mechanical trauma or disease, muscle is capable of regeneration. The process of regeneration mirrors that of myogenesis in the embryo—by fusion of myoblasts derived from the satellite cell population with each other and the damaged fibers. Regeneration of muscle fibers using normal myoblasts injected into diseased muscle (myoblasts transfer therapy or MTT) may be of use in treating inherited muscle diseases. Experimental MTT has already been studied in the disease Duchenne muscular dystrophy with disappointing results in human trials.

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