Myogenesis is the formation of skeletal muscular tissue , particularly during embryonic development .
101-419: Muscle fibers generally form through the fusion of precursor myoblasts into multinucleated fibers called myotubes . In the early development of an embryo , myoblasts can either proliferate , or differentiate into a myotube. What controls this choice in vivo is generally unclear. If placed in cell culture, most myoblasts will proliferate if enough fibroblast growth factor (FGF) or another growth factor
202-401: A BHLH-Pas transcription factor , inhibits transcription by active repression and displays enhanced expression in ventral limb muscle masses during chick and mouse embryonic development. It accomplishes this by repressing MyoD transcription by binding to the enhancer region, and prevents premature myogenesis. Delta1 expression in neural crest cells is necessary for muscle differentiation of
303-474: A skeleton . The skeletal muscle cells are much longer than in the other types of muscle tissue, and are also known as muscle fibers . The tissue of a skeletal muscle is striated – having a striped appearance due to the arrangement of the sarcomeres . A skeletal muscle contains multiple fascicles – bundles of muscle fibers. Each individual fiber, and each muscle is surrounded by a type of connective tissue layer of fascia . Muscle fibers are formed from
404-417: A complex interface region known as the musculotendinous junction also known as the myotendinous junction , an area specialised for the primary transmission of force. At the muscle-tendon interface, force is transmitted from the sarcomeres in the muscle cells to the tendon. Muscles and tendons develop in close association, and after their joining at the myotendinous junction they constitute a dynamic unit for
505-558: A higher capability for electrochemical transmission of action potentials and a rapid level of calcium release and uptake by the sarcoplasmic reticulum. The fast twitch fibers rely on a well-developed, anaerobic , short term, glycolytic system for energy transfer and can contract and develop tension at 2–3 times the rate of slow twitch fibers. Fast twitch muscles are much better at generating short bursts of strength or speed than slow muscles, and so fatigue more quickly. The slow twitch fibers generate energy for ATP re-synthesis by means of
606-757: A higher density of capillaries . However, muscle cells cannot divide to produce new cells, and as a result there are fewer muscle cells in an adult than in a newborn. There are a number of terms used in the naming of muscles including those relating to size, shape, action, location, their orientation, and their number of heads. Broadly there are two types of muscle fiber: Type I , which is slow, and Type II which are fast. Type II has two divisions of type IIA (oxidative), and type IIX (glycolytic), giving three main fiber types. These fibers have relatively distinct metabolic, contractile, and motor unit properties. The table below differentiates these types of properties. These types of properties—while they are partly dependent on
707-450: A lack of lateral migration. PAX3 mediates the transcription of c-Met and is responsible for the activation of MyoD expression—one of the functions of MyoD is to promote the regenerative ability of satellite cells (described below). PAX3 is generally expressed at its highest levels during embryonic development and is expressed at a lesser degree during the fetal stages; it is expressed in migrating hypaxial cells and dermomyotome cells, but
808-434: A lack of migration. LBX1 is responsible for the development and organization of muscles in the dorsal forelimb as well as the movement of dorsal muscles into the limb following delamination . Without LBX1, limb muscles will fail to form properly; studies have shown that hindlimb muscles are severely affected by this deletion while only flexor muscles form in the forelimb muscles as a result of ventral muscle migration. c-Met
909-450: A left-right desynchronization of the segmentation oscillations. Many studies with Xenopus and zebrafish have analyzed the factors of this development and how they interact in signaling and transcription. However, there are still some doubts in how the prospective mesodermal cells integrate the various signals they receive and how they regulate their morphogenic behaviours and cell-fate decisions. Human embryonic stem cells for example have
1010-458: A long term system of aerobic energy transfer. These mainly include the ATPase type I and MHC type I fibers. They tend to have a low activity level of ATPase, a slower speed of contraction with a less well developed glycolytic capacity. Fibers that become slow-twitch develop greater numbers of mitochondria and capillaries making them better for prolonged work. Individual muscles tend to be
1111-417: A mixture of various fiber types, but their proportions vary depending on the actions of that muscle. For instance, in humans, the quadriceps muscles contain ~52% type I fibers, while the soleus is ~80% type I. The orbicularis oculi muscle of the eye is only ~15% type I. Motor units within the muscle, however, have minimal variation between the fibers of that unit. It is this fact that makes
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#17328874331371212-435: A muscle cell. Consequently, the simultaneous deletion of Myf5 and MyoD also results in a complete lack of skeletal muscle formation. Research has shown that MyoD directly activates its own gene; this means that the protein made binds the myoD gene and continues a cycle of MyoD protein production. Meanwhile, Myf5 expression is regulated by Sonic hedgehog , Wnt1 , and MyoD itself. By noting the role of MyoD in regulating Myf5,
1313-468: A muscle, and are often termed as muscle fibers . A single muscle such as the biceps in a young adult male contains around 253,000 muscle fibers. Skeletal muscle fibers are multinucleated with the nuclei often referred to as myonuclei . This occurs during myogenesis with the fusion of myoblasts each contributing a nucleus. Fusion depends on muscle-specific proteins known as fusogens called myomaker and myomerger . Many nuclei are needed by
1414-456: A number of different environmental factors. This plasticity can, arguably, be the strongest evolutionary advantage among organisms with muscle. In fish, different fiber types are expressed at different water temperatures. Cold temperatures require more efficient metabolism within muscle and fatigue resistance is important. While in more tropical environments, fast powerful movements (from higher fast-twitch proportions) may prove more beneficial in
1515-463: A reliance on glycolytic enzymes. Fibers can also be classified on their twitch capabilities, into fast and slow twitch. These traits largely, but not completely, overlap the classifications based on color, ATPase, or MHC ( myosin heavy chain ). Some authors define a fast twitch fiber as one in which the myosin can split ATP very quickly. These mainly include the ATPase type II and MHC type II fibers. However, fast twitch fibers also demonstrate
1616-441: A role in muscle differentiation. The SIX1 gene plays a critical role in hypaxial muscle differentiation in myogenesis. In mice lacking this gene, severe muscle hypoplasia affected most of the body muscles, specifically hypaxial muscles. In myoblasts, PtdIns5P, produced by the lipid phosphatase MTM1, is rapidly metabolized by PI5P 4-kinase α into PI(4,5)P2, which accumulates at the plasma membrane. This accumulation facilitates
1717-483: A tendon. Multipennate muscles have fibers that are oriented at multiple angles along the force-generating axis, and this is the most general and most common architecture. Muscle fibers grow when exercised and shrink when not in use. This is due to the fact that exercise stimulates the increase in myofibrils which increase the overall size of muscle cells. Well exercised muscles can not only add more size but can also develop more mitochondria , myoglobin , glycogen and
1818-574: Is a tyrosine kinase receptor that is required for the survival and proliferation of migrating myoblasts. A lack of c-Met disrupts secondary myogenesis and—as in LBX1—prevents the formation of limb musculature. It is clear that c-Met plays an important role in delamination and proliferation in addition to migration. PAX3 is needed for the transcription of c-Met. Associated Genetic Factors: PAX3 , c-Met , Mox2 , MSX1 , Six, Myf5 , and MyoD Mox2 (also referred to as MEOX-2) plays an important role in
1919-482: Is a method used to study myogenesis, which manipulates a number of different techniques like high-throughput screening technologies, genome wide cell-based assays , and bioinformatics , to identify different factors of a system. This has been specifically used in the investigation of skeletal muscle development and the identification of its regulatory network. Systems approach using high-throughput sequencing and ChIP-chip analysis has been essential in elucidating
2020-400: Is a predominance of type II fibers utilizing glycolytic metabolism. Because of the discrepancy in fast twitch fibers compared to humans, chimpanzees outperform humans in power related tests. Humans, however, will do better at exercise in aerobic range requiring large metabolic costs such as walking (bipedalism). Across species, certain gene sequences have been preserved, but do not always have
2121-405: Is a slow twitch-fiber that can sustain longer contractions ( tonic ). In lobsters, muscles in different body parts vary in the muscle fiber type proportions based on the purpose of the muscle group. In the early development of vertebrate embryos, growth and formation of muscle happens in successive waves or phases of myogenesis . The myosin heavy chain isotype is a major determinant of
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#17328874331372222-735: Is associated with amplifying expression of genes that are already being expressed in the organism. Deleting myogenin results in nearly complete loss of differentiated muscle fibers and severe loss of skeletal muscle mass in the lateral/ventral body wall. Myf-6 (also known as MRF4 or Herculin) is important to myotube differentiation and is specific to skeletal muscle. Mutations in Myf-6 can provoke disorders including centronuclear myopathy and Becker muscular dystrophy . Associated genetic factors: LBX1 and Mox2 In specific muscle formation, mutations in associated genetic factors begin to affect specific muscular regions. Because of its large responsibility in
2323-499: Is attached to other organelles such as the mitochondria by intermediate filaments in the cytoskeleton. The costamere attaches the sarcomere to the sarcolemma. Every single organelle and macromolecule of a muscle fiber is arranged to ensure that it meets desired functions. The cell membrane is called the sarcolemma with the cytoplasm known as the sarcoplasm . In the sarcoplasm are the myofibrils. The myofibrils are long protein bundles about one micrometer in diameter. Pressed against
2424-505: Is expressed in other mammals, so is still accurately seen (along with IIB) in the literature. Non human fiber types include true IIb fibers, IIc, IId, etc. Further fiber typing methods are less formally delineated, and exist on more of a spectrum. They tend to be focused more on metabolic and functional capacities (i.e., oxidative vs. glycolytic , fast vs. slow contraction time). As noted above, fiber typing by ATPase or MHC does not directly measure or dictate these parameters. However, many of
2525-421: Is involved in the regulation of myogenesis. Specifically, it regulates the type of muscle fiber developed and its maturations. Low levels of TCF4 promote both slow and fast myogenesis, overall promoting the maturation of muscle fiber type. Thereby this shows the close relationship of muscle with connective tissue during the embryonic development. Regulation of myogenic differentiation is controlled by two pathways:
2626-624: Is not expressed at all during the development of facial muscle . Mutations in Pax3 can cause a variety of complications including Waardenburg syndrome I and III as well as craniofacial-deafness-hand syndrome . Waardenburg syndrome is most often associated with congenital disorders involving the intestinal tract and spine, an elevation of the scapula, among other symptoms. Each stage has various associated genetic factors without which will result in muscular defects. Associated Genetic Factors: c-Met / HGF and LBX1 Mutations in these genetic factors causes
2727-399: Is not the same as ATPase fiber typing. Almost all multicellular animals depend on muscles to move. Generally, muscular systems of most multicellular animals comprise both slow-twitch and fast-twitch muscle fibers, though the proportions of each fiber type can vary across organisms and environments. The ability to shift their phenotypic fiber type proportions through training and responding to
2828-404: Is preceded by the formation of connective tissue frameworks, usually formed from the somatic lateral plate mesoderm . Myoblasts follow chemical signals to the appropriate locations, where they fuse into elongated multinucleated skeletal muscle cells. Between the tenth and the eighteenth weeks of gestation, all muscle cells have fast myosin heavy chains; two myotube types become distinguished in
2929-533: Is present in the medium surrounding the cells. When the growth factor runs out, the myoblasts cease division and undergo terminal differentiation into myotubes. Myoblast differentiation proceeds in stages. The first stage involves cell cycle exit and the commencement of expression of certain genes. The second stage of differentiation involves the alignment of the myoblasts with one another. Studies have shown that even rat and chick myoblasts can recognise and align with one another, suggesting evolutionary conservation of
3030-548: Is regulated by a gene regulatory network that includes a member of the T-box family, tbx6, ripply1, and mesp-ba. Skeletal myogenesis depends on the strict regulation of various gene subsets in order to differentiate the myogenic progenitors into myofibers. Basic helix-loop-helix (bHLH) transcription factors, MyoD, Myf5, myogenin, and MRF4 are critical to its formation. MyoD and Myf5 enable the differentiation of myogenic progenitors into myoblasts, followed by myogenin, which differentiates
3131-410: Is the endoderm . The mesoderm forms mesenchyme , mesothelium and coelomocytes . Mesothelium lines coeloms . Mesoderm forms the muscles in a process known as myogenesis , septa (cross-wise partitions) and mesenteries (length-wise partitions); and forms part of the gonads (the rest being the gametes ). Myogenesis is specifically a function of mesenchyme . The mesoderm differentiates from
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3232-454: Is used in fiber typing vs. MHC typing, and some ATPase types actually contain multiple MHC types. Also, a subtype B or b is not expressed in humans by either method . Early researchers believed humans to express a MHC IIb, which led to the ATPase classification of IIB. However, later research showed that the human MHC IIb was in fact IIx, indicating that the IIB is better named IIX. IIb
3333-468: The axial , paraxial , intermediate , and lateral plate mesoderms . The axial mesoderm gives rise to the notochord . The paraxial mesoderm forms the somitomeres , which give rise to mesenchyme of the head, and organize into somites in occipital and caudal segments, and give rise to sclerotomes (cartilage and bone), and dermatomes (subcutaneous tissue of the skin). Signals for somite differentiation are derived from surroundings structures, including
3434-406: The dentin of teeth, the kidneys, and the adrenal cortex. During the third week, a process called gastrulation creates a mesodermal layer between the endoderm and the ectoderm. This process begins with the formation of a primitive streak on the surface of the epiblast. The cells of the layers move between the epiblast and the hypoblast, and begin to spread laterally and cranially. The cells of
3535-449: The erector spinae and small vertebral muscles, and are innervated by the dorsal rami of the spinal nerves . All other muscles, including those of the limbs are hypaxial, and innervated by the ventral rami of the spinal nerves. During development, myoblasts (muscle progenitor cells) either remain in the somite to form muscles associated with the vertebral column or migrate out into the body to form all other muscles. Myoblast migration
3636-476: The fusion of developmental myoblasts in a process known as myogenesis resulting in long multinucleated cells. In these cells the nuclei , termed myonuclei , are located along the inside of the cell membrane . Muscle fibers also have multiple mitochondria to meet energy needs. Muscle fibers are in turn composed of myofibrils . The myofibrils are composed of actin and myosin filaments called myofilaments , repeated in units called sarcomeres, which are
3737-458: The pectoral , and abdominal muscles ; intrinsic and extrinsic muscles are subdivisions of muscle groups in the hand , foot , tongue , and extraocular muscles of the eye . Muscles are also grouped into compartments including four groups in the arm , and the four groups in the leg . Apart from the contractile part of a muscle consisting of its fibers, a muscle contains a non-contractile part of dense fibrous connective tissue that makes up
3838-631: The phosphatidylinositol 3-kinase /Akt pathway and the Notch /Hes pathway, which work in a collaborative manner to suppress MyoD transcription. The O subfamily of the forkhead proteins ( FOXO ) play a critical role in regulation of myogenic differentiation as they stabilize Notch/Hes binding. Research has shown that knockout of FOXO1 in mice increases MyoD expression, altering the distribution of fast-twitch and slow-twitch fibers. Primary muscle fibers originate from primary myoblasts and tend to develop into slow muscle fibers. Secondary muscle fibers then form around
3939-580: The sarcolemma . The myonuclei are quite uniformly arranged along the fiber with each nucleus having its own myonuclear domain where it is responsible for supporting the volume of cytoplasm in that particular section of the myofiber. A group of muscle stem cells known as myosatellite cells , also satellite cells are found between the basement membrane and the sarcolemma of muscle fibers. These cells are normally quiescent but can be activated by exercise or pathology to provide additional myonuclei for muscle growth or repair. Muscles attach to tendons in
4040-442: The somites , through the Notch signaling pathway . Gain and loss of this ligand in neural crest cells results in delayed or premature myogenesis. The significance of alternative splicing was elucidated using microarrary analysis of differentiating C2C12 myoblasts. 95 alternative splicing events occur during C2C12 differentiation in myogenesis. Therefore, alternative splicing is necessary in myogenesis. Systems approach
4141-436: The tendon at each end. The tendons attach the muscles to bones to give skeletal movement. The length of a muscle includes the tendons. Connective tissue is present in all muscles as deep fascia . Deep fascia specialises within muscles to enclose each muscle fiber as endomysium ; each muscle fascicle as perimysium , and each individual muscle as epimysium . Together these layers are called mysia . Deep fascia also separates
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4242-438: The associated related changes, not a change in fiber type. There are numerous methods employed for fiber-typing, and confusion between the methods is common among non-experts. Two commonly confused methods are histochemical staining for myosin ATPase activity and immunohistochemical staining for myosin heavy chain (MHC) type. Myosin ATPase activity is commonly—and correctly—referred to as simply "fiber type", and results from
4343-443: The basic functional, contractile units of the muscle fiber necessary for muscle contraction . Muscles are predominantly powered by the oxidation of fats and carbohydrates , but anaerobic chemical reactions are also used, particularly by fast twitch fibers . These chemical reactions produce adenosine triphosphate (ATP) molecules that are used to power the movement of the myosin heads . Skeletal muscle comprises about 35% of
4444-668: The body of humans by weight. The functions of skeletal muscle include producing movement, maintaining body posture, controlling body temperature, and stabilizing joints. Skeletal muscle is also an endocrine organ . Under different physiological conditions, subsets of 654 different proteins as well as lipids, amino acids, metabolites and small RNAs are found in the secretome of skeletal muscles. Skeletal muscles are substantially composed of multinucleated contractile muscle fibers (myocytes). However, considerable numbers of resident and infiltrating mononuclear cells are also present in skeletal muscles. In terms of volume, myocytes make up
4545-409: The capability to also differentiate into bone or fat. In this way, satellite cells have an important role in not only muscle development, but in the maintenance of muscle through adulthood. During embryogenesis , the dermomyotome and/or myotome in the somites contain the myogenic progenitor cells that will evolve into the prospective skeletal muscle. The determination of dermomyotome and myotome
4646-402: The crucial interconnectedness of the two genetic factors becomes clear. Associated genetic factors: Myogenin , Mcf2 , Six, MyoD , and Myf6 Mutations in these associated genetic factors will prevent myocytes from advancing and maturing. Myogenin (also known as Myf4) is required for the fusion of myogenic precursor cells to either new or previously existing fibers. In general, myogenin
4747-402: The developing fetus – both expressing fast chains but one expressing fast and slow chains. Between 10 and 40 per cent of the fibers express the slow myosin chain. Mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm , and the inner layer
4848-454: The development of the notochord canal and the axial canal takes place between days 17 and 19, when the first three somites are formed. During the third week, the paraxial mesoderm is organized into segments. If they appear in the cephalic region and grow with cephalocaudal direction, they are called somitomeres. If they appear in the cephalic region but establish contact with the neural plate, they are known as neuromeres , which later will form
4949-542: The direct assaying of ATPase activity under various conditions (e.g. pH ). Myosin heavy chain staining is most accurately referred to as "MHC fiber type", e.g. "MHC IIa fibers", and results from determination of different MHC isoforms . These methods are closely related physiologically, as the MHC type is the primary determinant of ATPase activity. However, neither of these typing methods is directly metabolic in nature; they do not directly address oxidative or glycolytic capacity of
5050-531: The environment has served organisms well when placed in changing environments either requiring short explosive movements (higher fast twitch proportion) or long duration of movement (higher slow twitch proportion) to survive. Bodybuilding has shown that changes in muscle mass and force production can change in a matter of months. Some examples of this variation are described below. American lobster , Homarus americanus , has three fiber types including fast twitch fibers, slow-twitch and slow-tonic fibers. Slow-tonic
5151-414: The epiblast move toward the primitive streak and slip beneath it, in a process called "invagination". Some of the migrating cells displace the hypoblast and create the endoderm, and other cells migrate between the endoderm and the epiblast to create the mesoderm. The remaining cells form the ectoderm. After that, the epiblast and the hypoblast establish contact with the extraembryonic mesoderm until they cover
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#17328874331375252-399: The fascicles can vary in their relationship to one another, and to their tendons. These variations are seen in fusiform , strap , and convergent muscles . A convergent muscle has a triangular or fan-shape as the fibers converge at its insertion and are fanned out broadly at the origin. A less common example of a parallel muscle is a circular muscle such as the orbicularis oculi , in which
5353-438: The fiber. When "type I" or "type II" fibers are referred to generically, this most accurately refers to the sum of numerical fiber types (I vs. II) as assessed by myosin ATPase activity staining (e.g. "type II" fibers refers to type IIA + type IIAX + type IIXA ... etc.). Below is a table showing the relationship between these two methods, limited to fiber types found in humans. Subtype capitalization
5454-461: The fibers are longitudinally arranged, but create a circle from origin to insertion. These different architectures, can cause variations in the tension that a muscle can create between its tendons. The fibers in pennate muscles run at an angle to the axis of force generation. This pennation angle reduces the effective force of any individual fiber, as it is effectively pulling off-axis. However, because of this angle, more fibers can be packed into
5555-593: The fibers of a skeletal muscle. It is thought that by performing endurance type events for a sustained period of time, some of the type IIX fibers transform into type IIA fibers. However, there is no consensus on the subject. It may well be that the type IIX fibers show enhancements of the oxidative capacity after high intensity endurance training which brings them to a level at which they are able to perform oxidative metabolism as effectively as slow twitch fibers of untrained subjects. This would be brought about by an increase in mitochondrial size and number and
5656-580: The formation of podosome-like protrusions, where the fusogen Myomaker is localized, playing a crucial role in the spatiotemporal regulation of myoblast fusion. There are 3 types of proteins produced during myogenesis. Class A proteins are the most abundant and are synthesized continuously throughout myogenesis. Class B proteins are proteins that are initiated during myogenesis and continued throughout development. Class C proteins are those synthesized at specific times during development. Also 3 different forms of actin were identified during myogenesis. Sim2 ,
5757-435: The formation of satellite cells and, in turn, prevent postnatal muscle growth. Satellite cells are described as quiescent myoblasts and neighbor muscle fiber sarcolemma . They are crucial for the repair of muscle, but have a very limited ability to replicate. Activated by stimuli such as injury or high mechanical load, satellite cells are required for muscle regeneration in adult organisms. In addition, satellite cells have
5858-510: The great majority of skeletal muscle. Skeletal muscle myocytes are usually very large, being about 2–3 cm long and 100 μm in diameter. By comparison, the mononuclear cells in muscles are much smaller. Some of the mononuclear cells in muscles are endothelial cells (which are about 50–70 μm long, 10–30 μm wide and 0.1–10 μm thick), macrophages (21 μm in diameter) and neutrophils (12-15 μm in diameter). However, in terms of nuclei present in skeletal muscle, myocyte nuclei may be only half of
5959-403: The groups of muscles into muscle compartments. Two types of sensory receptors found in muscles are muscle spindles , and Golgi tendon organs . Muscle spindles are stretch receptors located in the muscle belly. Golgi tendon organs are proprioceptors located at the myotendinous junction that inform of a muscle's tension . Skeletal muscle cells are the individual contractile cells within
6060-467: The higher end of any sport tend to demonstrate patterns of fiber distribution e.g. endurance athletes show a higher level of type I fibers. Sprint athletes, on the other hand, require large numbers of type IIX fibers. Middle-distance event athletes show approximately equal distribution of the two types. This is also often the case for power athletes such as throwers and jumpers. It has been suggested that various types of exercise can induce changes in
6161-405: The human body, making up around 40% of body weight in healthy young adults. In Western populations, men have on average around 61% more skeletal muscle than women. Most muscles occur in bilaterally-placed pairs to serve both sides of the body. Muscles are often classed as groups of muscles that work together to carry out an action. In the torso there are several major muscle groups including
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#17328874331376262-429: The induction of mesoderm and regional specification . Impairing the function of Mox2 will prevent the proliferation of myogenic precursors and will cause abnormal patterning of limb muscles. Specifically, studies have shown that hindlimbs are severely reduced in size while specific forelimb muscles will fail to form. Myf5 is required for proper myoblast proliferation. Studies have shown that mice muscle development in
6363-432: The inside of the sarcolemma are the unusual flattened myonuclei. Between the myofibrils are the mitochondria . While the muscle fiber does not have smooth endoplasmic cisternae, it contains sarcoplasmic reticulum . The sarcoplasmic reticulum surrounds the myofibrils and holds a reserve of the calcium ions needed to cause a muscle contraction. Periodically, it has dilated end sacs known as terminal cisternae . These cross
6464-449: The intercostal and paraspinal regions can be delayed by inactivating Myf-5. Myf5 is considered to be the earliest expressed regulatory factor gene in myogenesis. If Myf-5 and MyoD are both inactivated, there will be a complete absence of skeletal muscle. These consequences further reveal the complexity of myogenesis and the importance of each genetic factor in proper muscle development. Associated Genetic Factors: Myf5 and MyoD One of
6565-424: The limbs. Some of the mesoderm derivatives include the muscle (smooth, cardiac, and skeletal), the muscles of the tongue (occipital somites), the pharyngeal arches muscle (muscles of mastication, muscles of facial expressions), connective tissue, the dermis and subcutaneous layer of the skin , bone and cartilage, dura mater, the endothelium of blood vessels , red blood cells , white blood cells , microglia ,
6666-549: The long run. In rodents such as rats, the transitory nature of their muscle is highly prevalent. They have high percentage of hybrid muscle fibers and have up to 60% in fast-to-slow transforming muscle. Environmental influences such as diet, exercise and lifestyle types have a pivotal role in proportions of fiber type in humans. Aerobic exercise will shift the proportions towards slow twitch fibers, while explosive powerlifting and sprinting will transition fibers towards fast twitch. In animals, "exercise training" will look more like
6767-530: The mechanisms involved. The third stage is the actual cell fusion itself. In this stage, the presence of calcium ions is critical. Fusion in humans is aided by a set of metalloproteinases coded for by the ADAM12 gene , and a variety of other proteins. Fusion involves recruitment of actin to the plasma membrane , followed by close apposition and creation of a pore that subsequently rapidly widens. Novel genes and their protein products that are expressed during
6868-460: The mesenchyme in the head. The somitomeres organize into somites which grow in pairs. In the fourth week, the somites lose their organization and cover the notochord and spinal cord to form the backbone. In the fifth week, there are 4 occipital somites, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral and 8 to 10 coccygeal that will form the axial skeleton. Somitic derivatives are determined by local signaling between adjacent embryonic tissues, in particular
6969-574: The most important stages in myogenesis determination requires both Myf5 and MyoD to function properly in order for myogenic cells to progress normally. Mutations in either associated genetic factor will cause the cells to adopt non-muscular phenotypes. As stated earlier, the combination of Myf5 and MyoD is crucial to the success of myogenesis. Both MyoD and Myf5 are members of the myogenic bHLH (basic helix-loop-helix) proteins transcription factor family. Cells that make myogenic bHLH transcription factors (including MyoD or Myf5) are committed to development as
7070-568: The movement of dorsal muscles into the limb following delamination, mutation or deletion of Lbx1 results in defects in extensor and hindlimb muscles. As stated in the Proliferation section, Mox2 deletion or mutation causes abnormal patterning of limb muscles. The consequences of this abnormal patterning include severe reduction in size of hindlimbs and complete absence of forelimb muscles. Associated genetic factors: PAX7 Mutations in Pax7 will prevent
7171-438: The muscle fiber from one side to the other. In between two terminal cisternae is a tubular infolding called a transverse tubule (T tubule). T tubules are the pathways for action potentials to signal the sarcoplasmic reticulum to release calcium, causing a muscle contraction. Together, two terminal cisternae and a transverse tubule form a triad . All muscles are derived from paraxial mesoderm . During embryonic development in
7272-536: The myoblast into myotubes. MRF4 is important for blocking the transcription of muscle-specific promoters, enabling skeletal muscle progenitors to grow and proliferate before differentiating. There are a number of events that occur in order to propel the specification of muscle cells in the somite. For both the lateral and medial regions of the somite, paracrine factors induce myotome cells to produce MyoD protein—thereby causing them to develop as muscle cells. A transcription factor ( TCF4 ) of connective tissue fibroblasts
7373-407: The myogenetic regulator RP58, and the tendon differentiation gene, Mohawk homeobox. Skeletal muscle#Skeletal muscle cells Skeletal muscle (commonly referred to as muscle ) is one of the three types of vertebrate muscle tissue , the other being cardiac muscle and smooth muscle . They are part of the voluntary muscular system and typically are attached by tendons to bones of
7474-468: The neck that show a potential inverse trend of fiber type percentages (one muscle has high percentage of fast twitch, while the complementary muscle will have a higher percentage of slow twitch fibers). The complementary muscles of turtles had similar percentages of fiber types. Chimpanzee muscles are composed of 67% fast-twitch fibers and have a maximum dynamic force and power output 1.35 times higher than human muscles of similar size. Among mammals, there
7575-536: The need for long durations of movement or short explosive movements to escape predators or catch prey. Skeletal muscle exhibits a distinctive banding pattern when viewed under the microscope due to the arrangement of two contractile proteins myosin , and actin – that are two of the myofilaments in the myofibrils . The myosin forms the thick filaments, and actin forms the thin filaments, and are arranged in repeating units called sarcomeres . The interaction of both proteins results in muscle contraction. The sarcomere
7676-411: The nephrotomes. In caudal regions, it forms the nephrogenic cord. It also helps to develop the excretory units of the urinary system and the gonads. The lateral plate mesoderm splits into the parietal (somatic) and visceral (splanchnic) layers. The formation of these layers starts with the appearance of intercellular cavities. The somatic layer depends upon a continuous layer with mesoderm that covers
7777-512: The neural tube, notochord, surface ectoderm and the somitic compartments themselves. The correct specification of the deriving tissues, skeletal, cartilage, endothelia and connective tissue is achieved by a sequence of morphogenic changes of the paraxial mesoderm, leading to the three transitory somitic compartments: dermomyotome, myotome and sclerotome. These structures are specified from dorsal to ventral and from medial to lateral. Each somite will form its own sclerotome that will differentiate into
7878-588: The next somite and then decreases as that somite is established. The notochord and the neural tube activate the protein SHH, which helps the somite to form its sclerotome. The cells of the sclerotome express the protein PAX1 that induces the cartilage and bone formation. The neural tube activates the protein WNT1 that expresses PAX 2 so the somite creates the myotome and dermatome. Finally, the neural tube also secretes neurotrophin 3, so that
7979-421: The notochord, neural tube , and epidermis . The intermediate mesoderm connects the paraxial mesoderm with the lateral plate. Eventually it differentiates into urogenital structures that consist of the kidneys, gonads, their associated ducts, and the adrenal cortex. The lateral plate mesoderm gives rise to the heart, blood vessels, and blood cells of the circulatory system, as well as to the mesodermal components of
8080-491: The nuclei present, while nuclei from resident and infiltrating mononuclear cells make up the other half. Considerable research on skeletal muscle is focused on the muscle fiber cells, the myocytes, as discussed in detail in the first sections, below. However, recently, interest has also focused on the different types of mononuclear cells of skeletal muscle, as well as on the endocrine functions of muscle, described subsequently, below. There are more than 600 skeletal muscles in
8181-612: The others. Most skeletal muscles in a human contain(s) all three types, although in varying proportions. Traditionally, fibers were categorized depending on their varying color, which is a reflection of myoglobin content. Type I fibers appear red due to the high levels of myoglobin. Red muscle fibers tend to have more mitochondria and greater local capillary density. These fibers are more suited for endurance and are slow to fatigue because they use oxidative metabolism to generate ATP ( adenosine triphosphate ). Less oxidative Type II fibers are white due to relatively low myoglobin and
8282-514: The potential to produce all of the cells in the body and they are able to self-renew indefinitely so they can be used for a large-scale production of therapeutic cell lines. They are also able to remodel and contract collagen and were induced to express muscle actin. This shows that these cells are multipotent cells. The intermediate mesoderm connects the paraxial mesoderm with the lateral plate mesoderm, and differentiates into urogenital structures . In upper thoracic and cervical regions, this forms
8383-461: The primary fibers near the time of innervation. These muscle fibers form from secondary myoblasts and usually develop as fast muscle fibers. Finally, the muscle fibers that form later arise from satellite cells. Two genes significant in muscle fusion are Mef2 and the twist transcription factor . Studies have shown knockouts for Mef2C in mice lead to muscle defects in cardiac and smooth muscle development, particularly in fusion. The twist gene plays
8484-452: The process are under active investigation in many laboratories. They include: There are a number of stages (listed below) of muscle development, or myogenesis. Each stage has various associated genetic factors lack of which will result in muscular defects. Associated Genetic Factors: PAX3 and c-Met Mutations in PAX3 can cause a failure in c-Met expression. Such a mutation would result in
8585-511: The process of somitogenesis the paraxial mesoderm is divided along the embryo 's length to form somites , corresponding to the segmentation of the body most obviously seen in the vertebral column . Each somite has three divisions, sclerotome (which forms vertebrae ), dermatome (which forms skin), and myotome (which forms muscle). The myotome is divided into two sections, the epimere and hypomere, which form epaxial and hypaxial muscles , respectively. The only epaxial muscles in humans are
8686-587: The properties of individual fibers—tend to be relevant and measured at the level of the motor unit, rather than individual fiber. Slow oxidative (type I) fibers contract relatively slowly and use aerobic respiration to produce ATP. Fast oxidative (type IIA) fibers have fast contractions and primarily use aerobic respiration, but because they may switch to anaerobic respiration (glycolysis), can fatigue more quickly than slow oxidative fibers. Fast glycolytic (type IIX) fibers have fast contractions and primarily use anaerobic glycolysis. The FG fibers fatigue more quickly than
8787-403: The rest of the embryo through intercellular signaling , after which the mesoderm is polarized by an organizing center . The position of the organizing center is in turn determined by the regions in which beta-catenin is protected from degradation by GSK-3. Beta-catenin acts as a co-factor that alters the activity of the transcription factor tcf-3 from repressing to activating, which initiates
8888-459: The same functional purpose. Within the zebrafish embryo, the Prdm1 gene down-regulates the formation of new slow twitch fibers through direct and indirect mechanisms such as Sox6 (indirect). In mice, the Prdm1 gene is present but does not control slow muscle genes in mice through Sox6 . In addition to having a genetic basis, the composition of muscle fiber types is flexible and can vary with
8989-399: The same muscle volume, increasing the physiological cross-sectional area (PCSA). This effect is known as fiber packing, and in terms of force generation, it more than overcomes the efficiency-loss of the off-axis orientation. The trade-off comes in overall speed of muscle shortening and in the total excursion. Overall muscle shortening speed is reduced compared to fiber shortening speed, as is
9090-524: The size principal of motor unit recruitment viable. The total number of skeletal muscle fibers has traditionally been thought not to change. It is believed there are no sex or age differences in fiber distribution; however, proportions of fiber types vary considerably from muscle to muscle and person to person. Among different species there is much variation in the proportions of muscle fiber types. Sedentary men and women (as well as young children) have 45% type II and 55% type I fibers. People at
9191-432: The skeletal muscle cell for the large amounts of proteins and enzymes needed to be produced for the cell's normal functioning. A single muscle fiber can contain from hundreds to thousands of nuclei. A muscle fiber for example in the human biceps with a length of 10 cm can have as many as 3,000 nuclei. Unlike in a non-muscle cell where the nucleus is centrally positioned, the myonucleus is elongated and located close to
9292-471: The somite creates the dermis. Boundaries for each somite are regulated by retinoic acid and a combination of FGF8 and WNT3a. So retinoic acid is an endogenous signal that maintains the bilateral synchrony of mesoderm segmentation and controls bilateral symmetry in vertebrates. The bilaterally symmetric body plan of vertebrate embryos is obvious in somites and their derivates, such as the vertebral column. Therefore, asymmetric somite formation correlates with
9393-526: The specific fiber type. In zebrafish embryos, the first muscle fibers to form are the slow twitch fibers. These cells will undergo migration from their original location to form a monolayer of slow twitch muscle fibers. These muscle fibers undergo further differentiation as the embryo matures. In larger animals, different muscle groups will increasingly require different fiber type proportions within muscle for different purposes. Turtles , such as Trachemys scripta elegans , have complementary muscles within
9494-446: The synthesis of gene products critical for mesoderm differentiation and gastrulation. Furthermore, mesoderm has the capability to induce the growth of other structures, such as the neural plate , the precursor to the nervous system. The mesoderm is one of the three germinal layers that appears in the third week of embryonic development . It is formed through a process called gastrulation . There are four important components, which are
9595-492: The tail. The mesoderm moves to the midline until it covers the notochord. When the mesoderm cells proliferate, they form the paraxial mesoderm. In each side, the mesoderm remains thin, and is known as the lateral plate. The intermediate mesoderm lies between the paraxial mesoderm and the lateral plate. Between days 13 and 15, the proliferation of extraembryonic mesoderm, primitive streak, and embryonic mesoderm take place. The notochord process occurs between days 15 and 17. Eventually,
9696-418: The targets of myogenic regulatory factors like MyoD and myogenin, their inter-related targets, and how MyoD acts to alter the epigenome in myoblasts and myotubes. This has also revealed the significance of PAX3 in myogenesis, and that it ensures the survival of myogenic progenitors. This approach, using cell based high-throughput transfection assay and whole-mount in situ hybridization , was used in identifying
9797-402: The tendon cartilage and bone component. Its myotome will form the muscle component and the dermatome that will form the dermis of the back. The myotome and dermatome have a nerve component. Surrounding structures such as the notochord, neural tube, epidermis and lateral plate mesoderm send signals for somite differentiation Notochord protein accumulates in presomitic mesoderm destined to form
9898-423: The total distance of shortening. All of these effects scale with pennation angle; greater angles lead to greater force due to increased fiber packing and PCSA, but with greater losses in shortening speed and excursion. Types of pennate muscle are unipennate , bipennate , and multipennate . A unipennate muscle has similarly angled fibers that are on one side of a tendon. A bipennate muscle has fibers on two sides of
9999-406: The transmission of force from muscle contraction to the skeletal system. Muscle architecture refers to the arrangement of muscle fibers relative to the axis of force generation , which runs from a muscle's origin to its insertion . The usual arrangements are types of parallel , and types of pennate muscle . In parallel muscles, the fascicles run parallel to the axis of force generation, but
10100-449: The various methods are mechanistically linked, while others are correlated in vivo . For instance, ATPase fiber type is related to contraction speed, because high ATPase activity allows faster crossbridge cycling . While ATPase activity is only one component of contraction speed, Type I fibers are "slow", in part, because they have low speeds of ATPase activity in comparison to Type II fibers. However, measuring contraction speed
10201-401: The yolk sac and amnion. They move onto either side of the prechordal plate . The prechordal cells migrate to the midline to form the notochordal plate. The chordamesoderm is the central region of trunk mesoderm. This forms the notochord, which induces the formation of the neural tube, and establishes the anterior-posterior body axis. The notochord extends beneath the neural tube from the head to
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