Developing muscle contains two types of myoblasts:  Early myoblasts are responsible for the formation of primary myotubes, chainlike structures that extend between tendons of the developing muscle. Primary myotubes are formed by nearly synchronous fusion of early myoblasts. Myotubes undergo further differentiation into mature skeletal muscle fibers. Primary myotubes observed in the light microscope exhibit a chain of multiple central nuclei surrounded by myofilaments.
 Late myoblasts give rise to secondary myotubes, which are formed in the innervated zone of developing muscle where the myotubes have direct contact with nerve terminals. Secondary myotubes continue to be formed by sequential fusion of myoblasts into the already-formed secondary myotubes at random positions along their length. Secondary myotubes are characterized by a smaller diameter, more widely spaced nuclei, and an increased number of myofilaments (Fig. 11.13). In the mature multinucleated muscle fiber, the nuclei are all in the peripheral sarcoplasm, just inside the plasma membrane.
Some nuclei that appear to belong to the skeletal muscle fiber are nuclei of satellite cells.
FIGURE 11.13 • Photomicrograph of developing skeletal muscle myotubes. This photomicrograph shows a cross section (on the left) and a longitudinal section (on the right) of developing skeletal muscle fibers in the stage of secondary myotubes. These myotubes are formed by sequential fusion of myoblasts, forming elongated tubular structures. Note that the myotubes have a small diameter and widely spaced, centrally positioned nuclei that gradually become displaced into the cell periphery by the increased number of newly synthesized myofilaments. In the mature multi-nucleated muscle fiber (upper left), all nuclei are positioned in the peripheral sarcoplasm, just inside the plasma cell membrane. 220.
Satellite cells are interposed between the plasma membrane of the muscle fiber and its external lamina. They are small cells with scant cytoplasm. The cytoplasm typically blends in with the muscle cell sarcoplasm when viewed in the light microscope, thus making them difficult to identify. Each satellite cell has a single nucleus with a chromatin network denser and coarser than that of muscle cell nuclei. Satellite cells are responsible for the skeletal muscle’s ability to regenerate, but their regenerative capacity is limited. These myogenic precursors of muscle cells are normally quiescent and do not express myogenic regulatory factors. However, after injury of muscle tissue, some satellite cells become activated, reenter the cell cycle, and begin to express MRFs. They proliferate and give rise to new myoblasts. As long as the external lamina remains intact, the myoblasts fuse within the external lamina to form myotubes, which then mature into a new fiber. In contrast, if the external lamina is disrupted, fibroblasts repair the injured site, with subsequent scar tissue formation.
Muscular dystrophies are characterized by progressive degeneration of skeletal muscle fibers, which places a constant demand on the satellite cells to replace the degenerated fibers. Ultimately, the satellite cell pool is exhausted. New experimental data indicate that, during this process, additional myogenic cells are recruited from the bone marrow and supplement the available satellite cells. The rate of degeneration exceeds the rate of regeneration, however, resulting in loss of muscle function. A future treatment strategy for muscular dystrophies may include the trans-plantation of satellite cells or their myogenic bone marrow counterparts into damaged muscle.
FIGURE 11.14 • Photomicrograph of longitudinally sectioned cardiac muscle. The arrows point to the intercalated discs. The disc represent specialized cell-to-cell attachments of the cardiac muscle cells. Also note the apparent branching of the muscle fibers. 360.