Myofibrillogenesis

Contractile myofibrils within myofibers extend the length of the myofiber and are composed of overlapping thick and thin filaments organized into repeating units called sarcomeres. Each sarcomere is bounded by perpendicular z-lines, which organize thin filaments and attach, via titin, to the thick filaments. Z-lines extend across the muscle cell and attach by transmembrane structures to the extracellular connective tissue. Sarcomeres, which are about 2.6-p.M long at rest, also serve as scaffolds for the sarcoplasmic reticulum, mitochondria, and metabolic enzymes. Myofibrillogenesis begins with aggregation of repeating units of thin filament (actin) and z-line proteins

Myoblasts Fuse And Myotubes Pictures

Fig. 1 Formation of myofibers during development. Myogenic determination results in three pools of precursor cells: embryonic myoblasts, fetal myoblasts and satellite cells. Myoblasts fuse into myotubes. Synthesis of contractile proteins and organiza tion of sarcomeres result in maturation into myofibers, which have a striated appearance under the microscope. Embryonic myoblasts form myofibers with slower contraction speeds and primarily aerobic metabolism. Fetal myoblasts organize adjacent to primary fibers and may form slow myofibers or myofibers with faster contraction and primarily anaerobic metabolism. Satellite cells proliferate; one of the daughter cells fusing with a myofiber to add myonuclei during postnatal hypertrophy or repair. (# Copyright 2003 by J. Novakofski.)

Fig. 1 Formation of myofibers during development. Myogenic determination results in three pools of precursor cells: embryonic myoblasts, fetal myoblasts and satellite cells. Myoblasts fuse into myotubes. Synthesis of contractile proteins and organiza tion of sarcomeres result in maturation into myofibers, which have a striated appearance under the microscope. Embryonic myoblasts form myofibers with slower contraction speeds and primarily aerobic metabolism. Fetal myoblasts organize adjacent to primary fibers and may form slow myofibers or myofibers with faster contraction and primarily anaerobic metabolism. Satellite cells proliferate; one of the daughter cells fusing with a myofiber to add myonuclei during postnatal hypertrophy or repair. (# Copyright 2003 by J. Novakofski.)

(a-actinin) beneath the sarcolemma of myotubes. Titin and then myosin are added as the nascent myofibrils migrate away from the sarcolemma and organize into sarcomeres. As muscle cells increase in length, new sarcomeres are added at the end of myofibrils.

FIBER TYPES

Myofiber type is defined by a combination of metabolic, contractile, and morphological characteristics. There are many possible combinations of characteristics but fiber type is most simply described as red (slow, oxidative, type I), intermediate (fast, oxidative and glycolytic, type IIa), or white (fast, glycolytic, type IIb). Most muscle proteins have fiber-type specific isoforms. Fiber-type characteristics are developmentally determined but may be modulated by subsequent neural, endocrine, and mechanical influences. Myosin heavy chain (MHC), an abundant fiber-type marker, undergoes a developmental transition from embryonic to neonatal to adult isoforms. Expression of different proteins with fiber-type specific isoforms is weakly coordinated in transitional fibers. In the embryo, slow primary fibers are larger than secondary fibers, but fast fibers become larger after birth.

MUSCLE HYPERTROPHY

The postnatal increase in myofiber size requires satellite cell fusion, DNA addition, and a protein synthesis rate greater than the rate of degradation. Newly formed myotubes are 5 10 mm in diameter, growing into 25 100 mm myofibers a several hundredfold increase in mass. Insulin-like growth factor-I (IGF-I) is the major factor stimulating hypertrophy. IGF-I activates a number of signaling pathways including the calcineurin pathway and the phosphotidylinositiol-3 kinase pathway that increases protein synthesis. The proteasome pathway degrades most muscle proteins.

MESODERM ORIGINS

Skeletal muscles of the head, back, abdomen, and limbs have different lineages in the embryo (Fig. 2). Muscles of the head originate directly from myoblasts of the cranial mesoderm. Myoblasts that form the muscles of the limbs and trunk originate in somites. Somites result from segmentation of the paraxial mesoderm along the neural tube and notochord. The dorsal portion of the somite forms the dermomyotome, whereas the ventral portion forms the sclerotome, which is subsequently induced to form axial skeleton. The dermomyotome then segments into an inner myotome layer and outer dermatome layer. Axial muscles (i.e., longissimus, psoas) derive from the dorsomedial or epaxial portion of the myotome, whereas abdominal muscles derive from the ventrolateral or hypaxial portion of the myotome. Limb muscles derive from precursors that migrate out of the ventrolateral myotome. Anterior somites develop before posterior somites so there is a temporal gradient in myoblast migration, and forelimbs develop before hindlimbs. After

Myotome For Iliopsoas

Fig. 2 Origin of muscles in the embryo. Muscles of the head, back, abdomen, and limbs arise from different developmental lineages, which are established early in embryonic development. Shaded areas in the drawing of the embryo give rise to muscles in the corresponding shaded locations of the mature animal. Muscles of the head and extraocular muscles originate from the cranial mesoderm, whereas muscles of the body and limbs derive from the myotomes on either side of the neural tube. Epaxial muscles develop from the dorsomedial portion of the myotome, whereas hypaxial muscles develop from the ventrolateral portion of the myotome. Myoblasts that form limb muscles delaminate from the ventrolateral myotome, migrate into the limbs, and undergo extensive proliferation before fusing into myofibers. Organization into individual muscles is directed by hox gene expression and signals from nearby mesoderm that will form connective tissue. (# Copyright 2003 by J. Novakofski.)

Fig. 2 Origin of muscles in the embryo. Muscles of the head, back, abdomen, and limbs arise from different developmental lineages, which are established early in embryonic development. Shaded areas in the drawing of the embryo give rise to muscles in the corresponding shaded locations of the mature animal. Muscles of the head and extraocular muscles originate from the cranial mesoderm, whereas muscles of the body and limbs derive from the myotomes on either side of the neural tube. Epaxial muscles develop from the dorsomedial portion of the myotome, whereas hypaxial muscles develop from the ventrolateral portion of the myotome. Myoblasts that form limb muscles delaminate from the ventrolateral myotome, migrate into the limbs, and undergo extensive proliferation before fusing into myofibers. Organization into individual muscles is directed by hox gene expression and signals from nearby mesoderm that will form connective tissue. (# Copyright 2003 by J. Novakofski.)

migration, myoblasts proliferate extensively at the location of presumptive muscles and aggregate into ventral and dorsal masses before individual muscles form. Positional clues for myoblast migration and subsequent formation of individual muscles within limbs are provided by hox gene expression and cartilage derived from the limb bud mesenchyme.

Hox Gene Expression Location

MYOGENIC DETERMINATION FACTORS

Formation of myofibers from mesenchymal precursors is controlled by growth factors that induce or inhibit

Fig. 3 Myogenesis and myogenic regulation. Each step leading to myofiber formation is controlled by growth factors that induce or inhibit myogenesis. Activators indicated by an arrow (!), inhibitors indicated by a bar (I ). Wnt, sonic hedge hog (Shh) and bone morphogenic proteins (BMP) are secreted from the neural tube, notochord and lateral ectoderm. These secreted growth factors induce expression of myogenic regulatory transcription factors (Pax3, Myf5 and MyoD) in somatic or axial mesoderm. Subsequently, proliferation of myoblasts is regulated by insulin like growth factor 1 (IGF I) and fibroblast growth factor (FGF). IGF I and integrin (a cell adhesion protein) induce expression of myogenic transcription factors, MRF4, and myogenin, essential for myoblast fusion. IGF I is unique because it stimulates both myoblast proliferation and differen tiation. Myostatin is a potent inhibitor of myoblast proliferation and myostatin inactivation results in the increased myofiber of double muscled cattle. The proinflammatory cytokine tumor necrosis factor a (TNFa) inhibits myoblast proliferation, fusion, and synthesis of muscle specific proteins, resulting in smaller muscles. (# Copyright 2003 by J. Novakofski.)

myogenic regulatory transcription factors (MRFs) mediating the steps in myogenesis (Fig. 3). Determination of somitic mesoderm cells into myoblasts begins with induction of Myf5 and MyoD in Pax-3 positive cells of the somite by growth factors from the neural tube, notochord, and ectoderm. Although there is functional overlap, Myf5 primarily determines epaxial and MyoD determines hypaxial myoblasts. Subsequent expression of MRF4 and myogenin in determined myoblasts mediates differentiation and fusion into myofibers. MyoD and myogenin remain expressed at lower levels in mature myofibers.

Myoblast proliferation and differentiation are mutually exclusive events so myofiber formation can be increased either by stimulating myoblast proliferation or by inhibiting myoblast differentiation. Proliferation stops before fusion because elevated MRFs inhibit cell cycle proteins including cyclin-dependent kinases (CDKs), pRB, and p21. Conversely, in proliferating myoblasts, MRF activity is suppressed by Id protein or CDK phosphorylation.

Satellite cell function depends on expression of the Pax7 transcription factor, which is closely related to the Pax3 essential for myogenic determination and myoblast migration. Myf5 and MyoD are upregulated in proliferating satellite cells, whereas myogenin and MRF4 are not expressed until differentiation and fusion. Satellite cell divisions are asymmetric with fusion of one daughter cell to a myofiber while the other remains an unfused satellite cell. Asymmetry results in the segregation of Numb and differential upregulation of Pax7 and MRFs.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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