Muscular System

Development of Skeletal Muscle

Limb and axial muscles of the trunk and head develop by epitheliomesenchymal transformation from myogenic precursor cells. Studies show that myogenic precursor cells originate from the somatic mesoderm and from the ventral dermomyotome of somites in response to molecular signals from nearby tissues ( Figs. 15.1 and 15.2 ).

The first indication of myogenesis (muscle formation) is elongation of the nuclei and cell bodies of mesenchymal cells as they differentiate into myoblasts. These primordial muscle cells soon fuse to form myotubes: elongated, multinucleated, cylindrical structures.

At the molecular level, these events are preceded by activation and expression of the genes of the MYOD family of muscle-specific, basic helix-loop-helix transcription factors (including MYOD, myogenin [MYOG], MYF5, and myogenic factor 6 [MYF6], formerly called myogenic regulatory factor 4 [MRF4]) in the precursor myogenic cells. Retinoic acid enhances skeletal myogenesis by upregulating the expression of mesodermal markers and myogenic regulatory factors. It has been suggested that signaling molecules from the ventral neural tube and notochord (e.g., SHH) and others from the dorsal neural tube (e.g., WNTs, bone morphogenetic protein 4 [BMP4]) and from overlying ectoderm (e.g., WNTs, BMP4) regulate the beginning of myogenesis and the induction of the myotome ( Fig. 15.3 ). Further muscle growth in the fetus results from the ongoing fusion of myoblasts and myotubes.

During or after fusion of the myoblasts, myofilaments develop in the cytoplasm of the myotubes. Other organelles characteristic of striated muscle cells, such as myofibrils , also form. As the myotubes develop, they become invested with external laminae (layers), which segregate them from the surrounding connective tissue. Fibroblasts produce the perimysium and epimysium layers of the fibrous sheath of the muscle; the endomysium is formed by the external lamina and reticular fibers.

Most skeletal muscles develop before birth, and almost all remaining muscles are formed by the end of the first year. The increase in the size of a muscle after the first year results from increased fiber diameter from the formation of more myofilaments. Muscles increase in length and width to grow with the skeleton. Their ultimate size depends on the amount of exercise that is performed. Not all embryonic muscle fibers persist; many of them fail to establish themselves as necessary units of the muscle and soon degenerate.

Myotomes

Each typical myotome part of a somite divides into a dorsal epaxial division and a ventral hypaxial division (see Fig. 15.1 B ). Every developing spinal nerve divides and sends a branch to each myotome division. The dorsal primary ramus supplies the epaxial division, and the ventral primary ramus supplies the hypaxial division. The myoblasts that form the skeletal muscles of the trunk are derived from mesenchyme in the myotome regions of the somites (see Fig. 15.1 ). Some muscles, such as the intercostal muscles, remain segmentally arranged like the somites, but most myoblasts migrate away from the myotome and form nonsegmented muscles.

Gene-targeting studies in the mouse embryo show that myogenic regulatory factors (MYOD, MYF6, MYF5, and MYOG) are essential for the development of the hypaxial, epaxial, abdominal, and intercostal muscles.

Myoblasts from epaxial divisions of the myotomes form the extensor muscles of the neck and vertebral column ( Fig. 15.4 ). The embryonic extensor muscles derived from the sacral and coccygeal myotomes degenerate; their adult derivatives are the dorsal sacrococcygeal ligaments . Myoblasts from the hypaxial divisions of the cervical myotomes form the scalene, prevertebral, geniohyoid, and infrahyoid muscles (see Fig. 15.4 ). The thoracic myotomes form the lateral and ventral flexor muscles of the vertebral column, and the lumbar myotomes form the quadratus lumborum muscle. The sacrococcygeal myotomes form the muscles of the pelvic diaphragm and probably the striated muscles of the anus and sex organs.