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Modification of growth and development of muscles of poultry.

Growth curves of selected and unselected lines of broilers and Japanese quail show that chicks respond to selection for 8-week or 4-week body mass, respectively, by increasing the exponential growth rate during the first 2 weeks after hatching. Comparative studies indicate that growth rate varies among species of birds according to adult body mass, developmental maturity of the chick at hatching, and the postnatal growth increments of the skeletal muscles of the legs. Differentiation of tissues leading to mature function apparently precludes embryonic function and decreases proliferation and growth. Precocial species, such as the domestic fowl, grow only one-quarter as fast, on average, as altricial species of the same size, whose chicks are less mature at hatching and depend more on parental care for food, warmth, and protection. Among precocial species, those whose legs have the smallest postnatal growth increments grow most rapidly overall. The domestic fowl is among the slowest growing of precocial species. Although diet quality may limit growth rate, this should not be a factor in selection programs, because high quality diets can be provided. Rate of food assimilation apparently also is limiting, but it can be increased experimentally by force feeding and presumably is sufficiently selectable so as not to limit breeding programs designed to increase growth rate. The response of broilers and quail to selection of body mass apparently affects the rate of proliferation of skeletal muscles during the early posthatching period. Muscle quality is not affected. There is inconclusive evidence of a shift in muscle cell nuclei from differentiated to proliferative pools in selected lines. Furthermore, selected broilers apparently are less capable than unselected chicks of generating body heat, which requires functional skeletal muscle during the first week posthatching. Growth performance of broilers might be increased beyond present levels by selecting directly for reduced or delayed maturity (e.g., thermogenesis, flight) of chicks during the first 2 weeks and by selecting smaller legs in adult birds. Any attempt to formulate a selection program on these ideas would require additional basic research and might be thwarted by economic considerations or by offsetting selection caused by phenotypic responses that strain certain functional relationships in the growing chick.

Animal Feed↗

Mechanical activity is necessary for the elimination of polyneuronal innervation of developing rat soleus muscles.

During early development, rat soleus muscle fibres are innervated by several axons. Neuromuscular activity is involved in the elimination of all but one terminal, but it is not clear whether electrical or mechanical activity is important. Here, we reduced mechanical activity only, by interfering with excitation-contraction coupling. Muscles treated with dantrolene sodium at 9 days produced significantly less force at 13 days of age than normal muscles, and their sensitivity to ACh was greater than that of controls. The elimination of polyneuronal innervation occurs between days 9-12, but in muscles treated with dantrolene, the loss of synapses was slower. Thus, reducing mechanical activity by interfering with excitation-contraction coupling, (a) delays muscle development and (b) reduces the rate of elimination of polyneuronal innervation.

Acetylcholine↗

Assembly of nebulin into the sarcomeres of avian skeletal muscle.

In developing muscle, relatively little is known about the synthesis and incorporation of the large actin binding protein, nebulin, into the sarcomere. To determine the temporal pattern of nebulin assembly into the myofibrils of differentiating skeletal muscle cells, myofibril assembly was examined by immunofluorescence microscopy. The distribution of nebulin was compared to other myofibrillar and cytoskeletal proteins (myosin, titin, actin, desmin, tubulin). At the onset of differentiation, we observed that nebulin is first seen in a diffuse distribution throughout the cytoplasm. At this time, muscle specific myosin and titin are also distributed in this manner. Myosin and titin become associated with the nascent myofibrils prior to the addition of nebulin. The mature striated pattern of myosin and titin also preceded the development of striations with nebulin. After nebulin becomes organized into a striated pattern, actin filaments separate across the A-band and form thin filaments of uniform length. These patterns of assembly suggest that nebulin is required for restricting the lengths of the thin filaments. We have employed the strategy of using ethyl methane sulfonate and taxol to perturb myofibril assembly to examine interactions critical for the addition of nebulin to the developing sarcomeres. The same temporal pattern of assembly seen in the normal cultures was observed in the ethyl methane sulfonate treated cultures, but at a much slower rate. In cultures treated with the microtubule stabilizing drug taxol, the amount of stress fibers and nascent I-bands was greatly diminished as previously reported by others; however, nebulin was found associated with myofibrils in a mature striated distribution. In addition, our results indicate that the taxol treated cultures contain remnants of the Z-line. These results suggest that nebulin assembly into the myofibril requires interactions or anchorage at the Z-line and within the A-band.

Animals↗

Development of muscle afferents in the spinal cord of the tammar wallaby.

The development of muscle afferents in the tammar wallaby was examined to address whether proprioceptive input contributes to the marked asymmetry of the fore and hindlimb movement. Anatomical tracing with biocytin showed that the muscle afferents had reached the brachial motor horn by postnatal day (P1), but were less advanced in the lumbar region. Labelled cells lying outside the motor horn, presumably filled via gap junctions, were evident in the neonatal lumbar cord. By the 4th postnatal week, the afferent innervation of both brachial and lumbar cords became similar. Afferent discharges from stretching the biceps muscle could be recorded at birth, but not until P4 from the hindlimb gastrocnemius muscle. The discharges were predominantly phasic until P35 when tonic activity could also be recorded. Short latency spinal reflex responses superimposed upon a longer lasting potential were present in the brachial cord at birth, appearing in the lumbar cord at P4. By the 3rd postnatal week, spinal reflex became comparable in both segmental levels. The time course of muscle afferent development was compared to the progression of natural cell death in the lumbar cord. Sensorimotor connections were established towards the end of the rapid phase cell death as observed in other vertebrates.

Action Potentials↗

Development and innervation of the abdominal muscle in embryonic Xenopus laevis.

The morphogenesis and innervation of the ventral abdominal musculature in Xenopus embryos was examined using microscopic techniques. Muscle development begins at Nieuwkoop and Faber Stage 31, when aggregates of undifferentiated cells form on the ventrolateral margins of rostral trunk myotomes. During subsequent stages, aggregates form and detach from progressively more caudal myotomes to form a series of seven discrete cell clusters (anlagen). The anlagen migrate ventrally in a cell-free space between the epidermis and a subepidermal layer of pigment cells. Extracellular aggregates of 30-nm granules are evident transiently between the migrating anlagen and the epidermis. During stages 39 and 40, each anlage transforms into a sheet of myotubes which attaches rostrally and caudally to adjacent sheets to form a seven-segmented muscle. The series of broad segments, approximately one fiber thick, extends from the pericardium to the level of the proctodeum. The embryonic muscle is innervated by the ventral rami of spinal nerves 2 to 9. The major nerve trunks to the muscle develop between stages 35/36 and 40. Axons initially grow ventrally along the paths taken by the muscle anlagen. When the anlagen become muscle segments, the nerves are deep to the narrow boundaries between the segments. Spinal nerve 2 ramifies in the first muscle segment and sends fibers rostrally to the geniohyoid muscle. The findings represent the first description of the development of this muscle in Xenopus and the first account of the development of the abdominal motor nerves in an amphibian embryo.

Abdominal Muscles↗

Examining the developing skeletal muscle: Why, what and how?

This review focuses on methodological concepts in the evaluation of skeletal muscle function, taking into account classical muscle physiology, the developing motor system in children and anthropometric parameters. Thereby, the classical concept of kinetic and thermodynamic description of muscle function is discussed in relation to data pertaining to human physiology. Emphasis is given to the specific problems that arise when assessing muscle function during development. Two important factors influencing muscle function are discussed in detail: changes in anthropometric characteristics and changes in co-ordinative skills in the developing individual. Finally, we discuss currently available methods for the evaluation of anaerobic muscle function in children and adolescents (maximal isometric grip force, peak jump force, peak jump power, Wingate test, Bosco test).

Adolescent↗

Myostatin knockout in mice increases myogenesis and decreases adipogenesis.

Growth differentiation factor-8 (GDF-8), or Myostatin, plays an important inhibitory role during muscle development. Since muscle and adipose tissue develop from the same mesenchymal stem cells, we hypothesized that Myostatin gene knockout may cause a switch between myogenesis and adipogenesis. Male and female wild type (WT) and Myostatin knockout (KO) mice were sacrificed at 4, 8, and 12 weeks of age. The gluteus muscle (GM) was larger in KO mice compared to WT mice at 8 (P < 0.01) and 12 (P < 0.001) weeks. At 12 weeks, KO mice had decreased fat depots (P < 0.01). Compared to 12-week-old WT mice, serum leptin concentration in KO mice was lower (P < 0.001) and leptin mRNA expression was decreased (P < 0.01) in inguinal adipose tissue. CCAAT/enhancer binding protein-alpha (C/EBPalpha) and peroxisome proliferator-activated receptor-gamma (PPARgamma) levels in adipose tissue were significantly lower in KO mice compared to WT mice. Thus, increased muscle development in Myostatin knockout mice is associated with reduced adipogenesis and consequently, decreased leptin secretion.

Adipose Tissue↗

Immunocytochemical analysis of fibre type differentiation in developing skeletal muscle.

Two monoclonal antibodies (McAbs) reactive with 'fast' and 'slow' adult myosin heavy chains have been produced and used in the analysis of human and rat muscle fibre type development. Expression of adult 'slow' myosin heavy chain was detected in human foetal muscle fibres as early as 14 weeks of gestation and in 1 day newborn rat muscle fibres. The standard histochemical stains used to show muscle fibre type do not distinguish fast from slow fibres at this early stage of development. These McAbs should therefore be of value in identifying factors involved in the differentiation of myotubes into fast and slow muscle fibres.

Adult↗

Flight muscles polymorphism in a flightless bug, Pyrrhocoris apterus (L.): developmental pattern, biochemical profile and endocrine control.

The flightless bug Pyrrhocoris apterus (L.) is polymorphic for both wing length and flight muscle development. The developed flight muscles of macropterous adults of both sexes first enlarge their volume during the first 5 days after adult emergence, but are then histolyzed in all males and females older than 10 and 14 days, respectively. The flight muscles of brachypterous adult males and females are underdeveloped due to their arrested growth. The total protein content of histolyzed dorsolongitudinal flight muscles from 21-day-old macropterous adults of both sexes is lower than that of developed dorsolongitudinal flight muscles in 5-10-days-old macropterous bugs, but substantially higher than the protein content of underdeveloped dorsolongitudinal flight muscles from adult brachypters. Histolyzed dorsolongitudinal flight muscles differ from the developed ones by decreased quantities of 18 electrophoretically separated proteins. Histolysis of developed dorsolongitudinal flight muscles is accompanied by significant decreases in citrate synthase, glyceraldehyde-3-phosphate dehydrogenase and beta-hydroxyacyl-CoA dehydrogenase enzyme activities and an increase in alanine aminotransferase activity, and can be precociously induced by application of a juvenile hormone analogue. This is the first report of flight muscle polymorphism, histolysis of developed flight muscles and its endocrine control in insects displaying non-functional wing polymorphism.

3-Hydroxyacyl CoA Dehydrogenases↗

Effects of soft diet on rat masseter muscle mitochondrial development.

There is not fine information regarding the influence of diet on development of masseter muscle and its mitochondria. Objective of this study is to compare mitochondrial enzyme activity, and morphology of masseter muscle fiber cells and its mitochondria prepared from rats fed soft diet to those fed hard diet. Cross-sectional area of fiber cells and number of mitochondria per unit area prepared from rats fed hard diet were greater than those of animals fed soft diet on postnatal day 60, and these differences decreased under both feeding conditions on days 120. Structure of mitochondrial cristae of rat fed hard diet was clear but that of fed soft diet ambiguous and contains many halos. Mitochondrial succinate-O2 and NADH-O2 oxidoreductase activities isolated from rats fed hard diet were higher than those of soft diet group over the period from days 30, and differences in both diet groups became the largest on days 60, and decreased on days 120. Our results indicated that development of masseter muscle fiber cells and mitochondria is hindered when rats are fed soft diet, but recover partially later, and hard diet is required for normal development of masseter muscle.

Animals↗

The early development of muscle spindle in human foetus.

The normal development of muscle spindles has been carefully described in a variety of species but only a few attempts were made to study the embryological development of the muscle spindle in humans. Most of the studies aimed to define the early development of muscle spindle in human foetuses, stated the begin of this process at the 11th week of intrauterine life, when the formation of a network of very fine nerve fibres with enlargements and ringle around developing muscle cells occur. In the present study we tried to document the probably earliest time of appearance of muscle spindles in the skeletal muscle of human foetuses. To this aim we examined fragments of deltoid and gastrocnemius muscles removed from human foetuses at the 9th and 10th week of gestation by using the light microscope technique. Data collected in muscle specimens at the 9th and 10th week of gestation showed the presence, at this time, of a structure with features clearly different from that of the adjacent muscular areas. This structure consists in a number of flat mesenchymal cells surrounding and forming several layers around a bundle of myoblasts smaller and lesser differentiated than the muscle cells located around and it is in close relationship with nervous fibres. These morphological findings might allow to identify the earliest stage of muscle spindle formation in human species.

Gestational Age↗

Developmental regulation of the mouse IGF-I exon 1 promoter region by calcineurin activation of NFAT in skeletal muscle.

Skeletal muscle development and growth are regulated through multiple signaling pathways that include insulin-like growth factor I (IGF-I) and calcineurin activation of nuclear factor of activated T cell (NFAT) transcription factors. The developmental regulation and molecular mechanisms that control IGF-I gene expression in murine embryos and in differentiating C2C12 skeletal myocytes were examined. IGF-I is expressed in developing skeletal muscle, and its embryonic expression is significantly reduced in embryos lacking both NFATc3 and NFATc4. During development, the IGF-I exon 1 promoter is active in multiple organ systems, including skeletal muscle, whereas the alternative exon 2 promoter is expressed predominantly in the liver. The IGF-I exon 1 promoter flanking sequence includes two highly conserved regions that contain NFAT consensus binding sequences. One of these conserved regions contains a calcineurin/NFAT-responsive regulatory region that is preferentially activated by NFATc3 in C2C12 skeletal muscle cells and NIH3T3 fibroblasts. This NFAT-responsive region contains three clustered NFAT consensus binding sequences, and mutagenesis experiments demonstrated the requirement for two of these in calcineurin or NFATc3 responsiveness. Chromatin immunoprecipitation analyses demonstrated that endogenous IGF-I genomic sequences containing these conserved NFAT binding sequences interact preferentially with NFATc3 in C2C12 cells. Together, these experiments demonstrated that a NFAT-rich regulatory element in the IGF-I exon 1 promoter flanking region is responsive to calcineurin signaling and NFAT activation in skeletal muscle cells. The identification of a calcineurin/NFAT-responsive element in the IGF-I gene represents a potential mechanism of intersection of these signaling pathways in the control of muscle development and homeostasis.

Animals↗

Does glucose 6-phosphatase regulate metabolic transformation in developing skeletal muscle?

Glycogen content and the activities of phosphorylase, phosphohexose isomerase, aldolase, glucose 6-phosphatase, succinate dehydrogenase, and alanine and aspartate amino-transferases have been biochemically determined in three gastrocnemii muscles of chick up to 9 weeks of postembryonic growth. Decline in glycogen, phosphorylase, phosphohexose isomerase and aldolase with a concomitant increase in succinate dehydrogenase reveals a switchover from glycolytic to oxidative metabolism in muscle. Activities of aminotransferases indicate the utilization of transamination products of alanine and aspartate in oxidative pathway. Transiently increased glucose 6-phosphatase seems to restrict glycogenolytic and glycolytic metabolism and thereby pave way for the acceleration of oxidative metabolism in developing muscle.

Alanine Transaminase↗

Association of titin and myosin heavy chain in developing skeletal muscle.

To understand molecular interactions that organize developing myofibrils, we examined the biosynthesis and interaction of titin and myosin heavy chain in cultures of developing muscle. Use of pulse-labeling, immunoprecipitation, and a reversible cross-linking procedure demonstrates that within minutes of synthesis, titin and myosin heavy chain can be chemically cross-linked into very large, detergent-resistant complexes retaining many features of intact myotubes. These complexes, predominantly of titin and myosin, occur very early in myofibrillogenesis as well as later. These data suggest that synthesis and assembly of titin and myosin are temporally and spatially coordinated in nascent myofibrils and support the hypothesis that titin molecules help to organize sarcomere formation.

Animals↗

Sodium and calcium components of the action potential in a developing skeletal muscle cell line.

1. Developmental changes in action potential properties were studied in a clonal rat skeletal muscle cell line. 2. Small action potentials were evoked in mononucleate myoblasts. No spike was seen in Na-free saline. A similar spike was evoked in a medium where all NaCl was replaced by LiCl. No spike was evoked when NaCl was replaced by CsCl. 3. Action potentials overshot zero membrane potential in multinucleate myotubes. The action potential was composed of two components, an initial fast spike and a hump on the falling phase or in some cases a distinct second peak. 4. Teh overshoot of the initial fast spike decreased when the external Na concentration was decreased. 5. In saline with 10 mM-Ca the second component often formed a distinct peak following the initial fast spike. A slow regenerative potential was evoked in Na-free media with a depolarizing current pulse. 6. In saline containing BaCl-2 instead of CaCl-2 there was always a second peak, the overshoot of which changed with external Ba concentration. A slow regenerative potential was evoked in Na-free, Ba-saline. The membrane conductance at the peak of the Ba-action potential was larger than in the resting state. 7. In adult rat skeletal muscle, the shape of the action potential was not changed when Ca was replaced by Ba. No action potential was evoked in Na-free Ba-saline or Ba-saline with tetrodotoxin (3 times 10-7 M). 8. The significance of the Ca component in the developing muscle is discussed.

Action Potentials↗

Developmental changes in the activation properties and ultrastructure of fast- and slow-twitch muscles from fetal sheep.

At early stages of muscle development, skeletal muscles contract and relax slowly, regardless of whether they are destined to become fast- or slow-twitch. In this study, we have characterised the activation profiles of developing fast- and slow-twitch muscles from a precocial species, the sheep, to determine if the activation profiles of the muscles are characteristically slow when both the fast- and slow-twitch muscles have slow isometric contraction profiles. Single skinned muscle fibres from the fast-twitch flexor digitorum longus (FDL) and slow-twitch soleus muscles from fetal (gestational ages 70, 90, 120 and 140 days; term 147 days) and neonatal (8 weeks old) sheep were used to determine the isometric force-pCa (pCa = -log10[Ca2+]) and force-pSr relations during development. Fast-twitch mammalian muscles generally have a greatly different sensitivity to Ca2+ and Sr2+ whereas slow-twitch muscles have a similar sensitivity to these divalent cations. At all ages studied, the force-pCa and force-pSr relations of the FDL muscle were widely separated. The mean separation of the mid-point of the curves (pCa50-pSr50) was approximately 1.1. This is typical of adult fast-twitch muscle. The force-pCa and force-pSr curves for soleus muscle were also widely separated at 70 and 90 days gestation (pCa50-pSr50 approximately 0.75); between 90 days and 140 days this separation decreased significantly to approximately 0.2. This leads to a paradoxical situation whereby at early stages of muscle development the fast muscles have contraction dynamics of slow muscles but the slow muscles have activation profiles more characteristic of fast muscles. The time course for development of the FDL and soleus is different, based on sarcomere structure with the soleus muscle developing clearly defined sarcomere structure earlier in gestation than the FDL. At 70 days gestation the FDL muscle had no clearly defined sarcomeres. Force (N cm-2) increased almost linearly between 70 and 140 days gestation in both muscle types and there was no difference between the Ca(2+)- and Sr(2+)-activated force throughout development.

Animals↗

A variant beta-tubulin isoform of Drosophila melanogaster (beta 3) is expressed primarily in tissues of mesodermal origin in embryos and pupae, and is utilized in populations of transient microtubules.

The beta 3-tubulin gene of Drosophila melanogaster codes for a variant tubulin isoform which is expressed at two distinct times during development: (1) during midembryogenesis from 8-16 hr postfertilization, and (2) during the 4 days of pupal development. We have determined the spatial pattern of beta 3-tubulin expression by localizing the beta 3 mRNA in paraffin sections using a 3' message-specific RNA probe and by localizing the beta 3 protein using a polyclonal antibody specific for Drosophila beta 3-tubulin. During embryogenesis beta 3 is restricted to and is expressed in all of the developing muscles. During pupal development beta 3 is also expressed at high levels in developing adult muscles. In addition, early in pupal development beta 3 is expressed in the imaginal discs, while at later times beta 3 is expressed in the epidermal cells of the wing blade, the optic lobe, the ovaries, and the testes. The expression of beta 3 tubulin ceases by the end of pupal development in all of these tissues except the ovaries and testes where expression persists into the adult. In both developing muscles and wings our results indicate that beta 3-tubulin is utilized in populations of specialized but transient cytoskeletal microtubules which are involved in establishing the final form of the tissue.

Animals↗