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| To understand muscle regulation it is necessary to understand its origin and development. Muscle is derived from proliferating cells that originate from the mesenchyme germ layer in the developing embryo. These cells are 'determined' into the muscle lineage and then become myoblasts. Myoblasts can leave the cell cycle and differentiate into a mature muscle cell phenotype. Differentiation involves the sequential activation of muscle-specific genes including contractile proteins by DNA-binding transcriptional regulator proteins from the family of Myogenic Regulatory Factors (MRFs). Terminally differentiated myoblasts in the heart are called cardiac myocytes; these cells remain single or
bi-nucleated throughout life. To date, no myogenic stem cells have been found in cardiac muscle, which may explain the limited regenerative capacity of the heart after injury.
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| Smooth muscle myoblasts also differentiate into mature smooth muscle cells (SMC), but unlike heart and skeletal muscle they are not terminally differentiated. SMC phenotype also varies, based on its location and function. SMCs are found throughout the body in the vascular wall, and retain the ability to proliferate, e.g. in response to hypertension or during angiogenesis.
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| Skeletal muscle cells differ from the other muscle types in that they are multi-nucleated. Proliferating myoblasts fuse and terminally differentiate to form a multinucleated myotube. Innervation by a motor nerve end plate induces the myotube to take on mature muscle fiber characteristics. Satellite cells are undifferentiated muscle precursor cells, found only in skeletal muscle. Since muscle fiber nuclei are post-mitotic, satellite cell proliferation and differentiation are critical events for postnatal muscle growth and regeneration after damage. Alterations in satellite cell differentiation with advancing age or in wasting syndromes are thought to contribute to skeletal muscle loss under these conditions.
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