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1 Muscular System There are three types of muscle, skeletal, cardiac, and smooth muscle. Almost all skeletal muscle is derived from the somites or somitomeres of the paraxial mesoderm. Splanchnic (lateral plate) mesoderm gives rise to the musculature of the heart and smooth muscle of the gut and respiratory tract. Smooth muscle of the blood vessels and arrector pili are derived from local mesoderm. Skeletal Muscle Virtually all skeletal muscle originates in somites or somitomeres. Precursors of most muscle lineages (myogenic cells) have been develop from the myotome of the somite. Myogenic cells pass through several additional mitotic divisions before completing a terminal mitotic division and becoming postmitotic myoblasts. Proliferating myogenic cells are kept in the cell cycle through the action of growth factors. Under the influence of other growth factors the post mitotic myoblasts begin to transcribe the mRNA's for the major contractile proteins actin and myosin. The result in the life cycle of a post mitotic myoblast is its fusion with other similar cells into a multinucleated myotube. Myotubes are extensively involved in mRNA and protein synthesis. In addition to forming actin and myosin, they synthesize many other proteins of muscle contraction: troponin and tropomyosin. The protein myofibrils assemble into ordered structures called sarcomeres. As myofibrils fill the myotubes, the nuclei of the myotubes migrate from a central to a peripheral position in the myotube. At this stage the myotube is considered to have differentiated into its terminal structure, a muscle fiber. The myonuclei of the multinucleated muscle fibers are no longer able to proliferate, but the muscle fiber must continue to grow in proportion of the growth of the fetus. This growth is accomplished with myogenic cells, called satellite cells, which take up positions between the muscle fiber and the basal lamina that each muscle fiber produces and encases itself within. Satellite cells divide slowly during the growth of an individual. Some daughter satellite cells fuse with the muscle fiber so that the muscle fiber contains an adequate number of nuclei to direct continuing synthesis of contractile proteins. In mature skeletal muscle, satellite cells persist as a source of muscle repair. They are a small population of mononucleated cells in the basal lamina of mature muscle fibers. Capillary sprouts grow into the forming muscle and motor nerve fibers enter shortly after the first myoblasts begin forming myotubes. All skeletal muscle fibers are not the same. Some will become slow twitch type I fibers and others will become fast twitch type II fibers. Also, there are other isoforms of muscle fibers. The twitch speeds are related to fast and slow forms of the myosin heavy chain subunits. The myosin molecules possess adenosinetriphosphatase activity, and differences in this activity partly account for the differences in the speed of contraction between fast and slow muscle fibers. It appears that fast and slow muscle fibers have information on their surfaces that determine whether fast or slow motor nerves make permanent contact. The nerves do not determine if the muscle fibers will be fast or slow twitch. At first, a motor nerve may terminate on both fast and slow muscle fibers, but eventually, incorrect linkages are broken. Hence, fast nerve fibers innervate only fast muscle fibers and slow nerves innervate only slow muscle fibers. 2 Skeletal Muscle of the Trunk and Limbs After their origin from somites, the muscle promordia become organized into well-defined groups and layers. In the thorax and abdomen, the intrinsic extensor muscles of the vertebral column (epaxial muscles) are derived from cells arising in the dorsal lip, whereas ventrolateral muscles (hypaxial muscles) arise from the epithelially organized ventral buds of the somites. In the limb regions, myogenic cells migrate from the epithelium of the ventrolateral dermomyotome. More cranial myogenic cells originating in similar regions of the occipital somites migrate into the developing tongue and diaphragm. At lumbar levels, precursors of the abdominal muscles also move out from the epithelium of ventrolateral somitic buds. In prunebelly syndrome, there is an absence of abdominal musculature due to deficiencies of certain signaling molecules in the dermomyotome. By the end of the fifth week, muscle cells are collected into a small dorsal portion, the epimere and a larger ventral portion, the hypomere. While this is occurring, nerves innervating segmental muscles are also divided into a dorsal primary ramus for the epimere and a ventral primary ramus for the hypomere. Myoblasts of the epimere form the extensor muscles of the vertebral column and those of the hypomere give rise to muscles of the body wall. Myoblasts from cervical hypomeres form the scalene, geniohyoid, infrahyoid, and prevertebral muscles. Those from thoracic segments split into three layers to form the external, internal, and innermost intercostal muscles. In the abdominal wall is formed the external oblique, internal oblique, transversus abdominis, and rectus abdominis muscles. Myoblasts from the hypoblast in the lumbar segments form the quadratus lumborum muscle, and those in the sacral and coccygeal region form the pelvic diaphragm and striated muscles of the anus. Skeletal Muscle of the Head Skeletal muscle of the head and neck is also mesodermal in origin. As with muscles in the trunk, muscles in the head and neck arise by the movement of myogenic cells away from the paraxial mesoderm through mesenchyme (either neural crest or mesodermal) on their way to their final destination. Morphogenesis of cranial muscles appears to be determined by information inherent in the connective tissues that ensheathe the muscles. Certain muscles in the head, like the tongue, arise from occipital somites in the manner of trunk muscles. Their more caudal level of origin is evidenced in the innervation by the hypoglossal nerve, which according to some comparative anatomists, appears to be a series of highly modified spinal nerves. Anomalies of skeletal muscle – Muscular dystrophy is a family of genetic diseases characterized by degeneration and regeneration of various muscle groups. In Duchenne muscular dystrophy, occurring in young boys, a membrane-associated protein called dystrophin is lacking in muscle fibers. Cardiac Muscle Derived from splanchnic (lateral plate) mesoderm of the early embryo, cardiac muscle cells arise from cells present in the myocardium. Differences between cardiac and skeletal muscle appear early. Immature cardiac and skeletal muscle cells do express isoforms of molecules that are characteristic of mature cells of each other. For example, both cardiac and skeletal muscle cells 3 in the embryo express high levels of cardiac α-actin. Skeletal muscle has its own skeletal αactin. Myosin associates with actin (F-actin), a filamentous polymer of globular G-actin molecules, to produce contraction of muscle. The ends of F-actin are anchored to the Z-lines with α-actinin a component of the Z line. After birth, expression of cardiac α-actin declines in skeletal muscle, while remaining elevated in cardiac muscle. In the adult, if there is cardiac hypertrophy, cardiac muscles begin to express large amounts of skeletal α-actin. Skeletal muscles hypertrophy when exercised. Cardiac hypertrophy may occur when there is a pathology, genetic defect, or chronic hypertension. Mononucleated cardiac myocytes face the problem of continued mitosis while continuing to contract. Cardiac myocytes deal with this problem by partially disassembling their contractile filaments during mitosis. In contrast to skeletal muscle, cardiac myocytes do not undergo fusion but rather remain as individual cells, although some may become binucleated. Cardiac myocytes keep close structural and functional contact through intercalated discs. Later, a network of cardiac muscle cells differentiates into an alternative pathway. These cells are characterized by increased size, a reduction in myofibrils, and a greatly increased concentration cytosolic glycogen. These cells form the conducting system, the Purkinje fibers. Smooth Muscle As with cardiac muscle, much of the smooth muscle on the body arises from splanchnic (lateral plate) mesoderm. Exceptions are the ciliary muscle and sphincter pupillae of the eye, which are derived from neural crest ectoderm. Another exception is most of the vascular smooth muscle, which frequently arises from local mesoderm. Smooth muscles have cells single nuclei. Questions 1. Smooth muscle of the heart and gut are derived from which of the following? a. paraxial mesoderm b. splanchnic mesoderm c. intermediate mesoderm d. local mesoderm 2. Myoblasts eventually migrating to the limbs and trunk derive from __________. a. sclerotomes b. lateral plate mesoderm c. dermatomes d. myotomes 3. Which of the following reasons describes why adult muscle cells are multinucleated? a. Myoblasts are initially multinucleated. b. Myotubes fuse to form myoblasts. c. Myotubes only replicate their nuclei and not the cytoplasm. d. Myoblasts fuse together to form myotubes. 4 4. Accessory cells that help repair muscle damage are called _________ cells. a. satellite b. Purkinje c. neural crest d. germ 5. The hypomere will give rise to which for the following muscle groups. a. Extensors of the vertebral column. b. Muscle of the gut. c. Muscle of the body wall and limbs. d. The arrector pili. 6. Epimeres can give rise to the ______________ muscles. a. pectoralis b. scalene c. erector spinae d. diaphragm 7. Occipital somites may give rise to the ___________ muscle. a. scalene b. iris c. suboccipital triangle d. tongue 8. Which of the following has intercalated discs? a. smooth muscle b. cardiac muscle c. skeletal muscle d. iris muscle 9. Purkinje fibers are _________ cells with large amounts of glycogen. a. cardiac muscle b. neural crest c. mesodermal d. nerve cells 10. Vascular smooth muscle arises from ___________. a. sclerotomes b. dermatomes c. local mesoderm d. neural crest cells