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The role of platelet-derived growth factor in turkey skeletal muscle development.

The role of platelet-derived growth factor (PDGF) isoforms in the proliferation of turkey skeletal muscle cells was examined using turkey myogenic cells. To compare the effects of PDGF during different developmental stages, postnatal myogenic satellite cell and embryonic myoblast cultures were developed for in vitro comparisons. Satellite cell cultures from turkeys selected and unselected for skeletal muscle accretion rates were also established to compare the role of PDGF in turkeys with different genetic origins. The results demonstrated that the BB and AB isoforms of PDGF enhanced satellite cell and embryonic myoblast proliferation, while the AA isoform had no effect. Satellite cells and embryonic myoblasts were more responsive to the BB isoform than to the AB isoform. Competitive binding assays demonstrated that there were no differences between PDGF receptor affinities or receptor numbers on either embryonic myoblasts and satellite cells or satellite cells derived from selected and unselected turkeys. The results suggest that PDGF may be an important mitogenic factor in turkey skeletal muscle development.

Animals↗

FGF5 stimulates expansion of connective tissue fibroblasts and inhibits skeletal muscle development in the limb.

FGF5 is expressed in the mesenchyme and skeletal muscle of developing and adult mouse limbs. However, the function of FGF5 during development of the limb and limb musculature is unknown. To elucidate the inherent participation of FGF5 during limb organogenesis, a retroviral delivery system (RCAS) was used to overexpress human FGF5 throughout developing hind limb of chicken embryos. Misexpression of the soluble growth factor severely inhibited the formation of mature myocytes. Limbs infected with RCAS-FGF5 contained smaller presumptive muscle masses as evidenced by a decrease in MyoD and myosin heavy chain expressing cells. In contrast, ectopic expression of FGF5 significantly stimulated proliferation and expansion of the tenascin-expressing, connective-tissue fibroblast lineage throughout the developing limb. Histological analysis demonstrated that the increase in tenascin immunostaining surrounding the femur, ileum, and pubis in the FGF5 infected limbs corresponded to the fibroblasts forming the stacked-cell perichondrium. Furthermore, pulse labeling experiments with the thymidine analog, BrdU, revealed that the increased size of the perichondrium was attributable to enhanced cell proliferation. These results support a model whereby FGF5 acts as a mitogen to stimulate the proliferation of mesenchymal fibroblasts that contribute to the formation of connective tissues such as the perichondrium, and inhibits the development of differentiated skeletal muscle. These results also contend that FGF5 is a candidate mediator of the exclusive spatial patterning of the hind limb connective tissue and skeletal muscle.

Animals↗

Leech filamin and Tractin: markers for muscle development and nerve formation.

The Lan3-14 and Laz10-1 monoclonal antibodies recognize a 400 kDa antigen that is specifically expressed by all muscle cells in leech. We show that the antigen recognized by both antibodies is a member of the filamin family of actin binding proteins. Leech filamin has two calponin homology domains and 35 filamin/ABP-repeat domains. In addition, we used the Laz10-1 antibody to characterize the development of the segmentally iterated dorsoventral flattener muscles. We demonstrate that the dorsoventral flattener muscle develops as three discrete bundles of myofibers and that CNS axons pioneering the DP nerve extend only along the middle bundle. Interestingly, the middle dorsoventral muscle anlage is associated with only non-neuronal expression of the L1-family cell adhesion molecule Tractin. This expression is transient and occurs at the precise developmental stages when DP nerve formation takes place. Based on these findings we propose that the middle dorsoventral muscle anlagen provides a substrate for early axonal outgrowth and nerve formation and that this function may be associated with differential expression of distinct cell adhesion molecules.

Animals↗

Duchenne dystrophic muscle develops lesions in long-term coculture with mouse spinal cord.

When strips of human skeletal muscle from biopsies of normal children and donors with Duchenne muscular dystrophy (DMD) are explanted in organotypic coculture with fetal mouse spinal cord, many regenerating muscle fibers develop, become innervated, and maintain a remarkable degree of mature structure and function for more than 3-6 months in vitro. Sequential light microscopy in correlation with electron-microscopic and electrophysiologic analyses showed that despite cross-species innervation, these human muscle fibers develop stable cross-striations, peripherally positioned myonuclei, and mature, functional motor endplates. Of special interest is the onset of significant progressive abnormalities, e.g., unusual focal myofibrillar lesions, in substantial numbers of innervated mature DMD muscle fibers after 2-4 months in culture. The focal myofibrillar lesions were not detected in normal muscle fibers maintained as long as 6 months in coculture, nor are they comparable to the generalized loss of cross-striations observed in muscle atrophy following in vitro denervation of mature DMD fibers.

Animals↗

Role of methylation in maintenance of positionally restricted transgene expression in developing muscle.

In transgenic mouse embryos, expression of a muscle-specific reporter, consisting of a chloramphenicol acetyltransferase gene linked to regulatory sequences from the rat myosin light chain 1/3 locus (MLC-CAT), is graded in developing axial muscles along the rostrocaudal axis and in cell cultures derived from these muscles. Here we demonstrate that maintenance of positional differences in MLC-CAT transgene expression cannot be attributed to differences in the transcriptional competence of corresponding muscles. Rather, patterns of transgene expression are reflected in the extent of CpG demethylation of both MLC1 promoter and MLC enhancer sequences. Variations in reporter gene expression can be reconstituted by in vitro methylation of specific CpGs in transfected MLC-CAT DNA. As the MLC-CAT transgene is activated during embryogenesis, demethylation of the MLC1 promoter lags behind that of the downstream MLC enhancer, which appears to be the initial target for epigenetic modification. In developing somites, demethylation of the transgenic MLC enhancer is not graded and therefore does not reflect early regional differences in MLC-CAT transgene expression patterns. These studies implicate selective methylation in the maintenance rather than in the establishment of transcriptional differences in developing muscles.

Animals↗

Is ribosomal capacity a potential metabolic marker of muscle development? Measurement by muscular biopsy.

Metabolic markers of muscle metabolism could help geneticists and nutritionists predict the breast meat development of chickens. The aim of the current study was to test the ribosomal capacity (CS), a potential metabolic marker, and to evaluate a simple biopsy method on the pectoralis major muscle. Ribosomal capacity was measured in three commercial meat chicken genotypes differing in their growth rate. Fast-, medium-, and slow-growing male chickens were fed using three commercial dietary programs of increasing energy and protein concentration (nine treatments). Biopsy was performed at 4 wk of age on the p. major 12 chickens per treatment. Fast-, medium-, and slow-growing chickens were slaughtered at market weight, i.e., 6, 8, and 12 wk of age, respectively, and breast meat (right and left p. major + minor) was dissected. A significant reduction in BW at slaughter (-1 to -3%) and breast meat yield (-4%) occurred only in biopsied medium-growing chickens but not in the other two types. Slow-growing chickens had a significantly lower CS (8.75 microg/mg) than the two other chicken types (9.40 and 9.46 microg/mg for fast- and medium-growing chickens, respectively). No significant dietary effect or interaction of dietary treatment with genotype was measured. The CS was not significantly correlated to breast meat development. Under conditions of the present experiment, CS may not be a relevant marker of subsequent breast meat development at 4 wk of age. The biopsy technique can easily be applied to other markers.

Aging↗

Heparan sulfate 6-o-sulfotransferase is essential for muscle development in zebrafish.

Heparan sulfate proteoglycans function in development and disease. They consist of a core protein with attached heparan sulfate chains that are altered by a series of carbohydrate-modifying enzymes and sulfotransferases. Here, we report on the identification and characterization of a gene encoding zebrafish heparan sulfate 6-O-sulfotransferase (hs6st) that shows high homology to other heparan sulfate 6-O-sulfotransferases. When expressed as a fusion protein in cultured cells, the protein shows specific 6-O-sulfotransferase activity and preferentially acts on the iduronosyl N-sulfoglycosamine. In the developing embryo, hs6st is expressed in the brain, the somites, and the fins; the same structures that were affected upon morpholino-mediated functional knockdown. Morpholino injections significantly inhibited 6-O- but not 2-O-sulfation as assessed by HPLC. Morphants display disturbed somite specification independent of the somite oscillator mechanism and have impaired muscle differentiation. In conclusion, our results show that transfer of sulfate to specific positions on glycosaminoglycans is essential for muscle development.

Amino Acid Sequence↗

Mutations in the rotated abdomen locus affect muscle development and reveal an intrinsic asymmetry in Drosophila.

In bilateral animals, the left and right sides of the body usually present asymmetric structures, the genetic bases of whose generation are still largely unknown [CIBA Foundation (1991) Biological Asymmetry and Handedness, CIBA Foundation Symposium 162 (Wiley, New York), pp. 1-327]. In Drosophila melanogaster, mutations in the rotated abdomen (rt) locus cause a clockwise helical rotation of the body. Even null alleles are viable but exhibit defects in embryonic muscle development, rotation of the whole larval body, and helical staggering of cuticular patterns in abdominal segments of the adult. rotated abdomen is expressed in the embryonic mesoderm and midgut but not in the ectoderm; it encodes a putative integral membrane glycoprotein (homologous to key yeast mannosyltransferases). Mesodermal cells defective in O-glycosylation lead to an impaired larval muscular system. We propose that the staggering of the adult abdominal segments would be a consequence of the relaxation of intrinsic rotational torque of muscle architecture, preventing the colateral alignment of the segmental histoblast cells during their proliferation at metamorphosis.

Amino Acid Sequence↗

Semitendinosis muscle development in several strains of fetal and perinatal pigs.

At 110 d of gestation, fetuses were removed from Ossabaw, Yorkshire and crossbred sows and from sows selected for high (obese) or for low (lean) backfat thickness. Ossabaw and obese fetuses were smaller than lean, Yorkshire and crossbred fetuses (595 +/- 32 and 863 +/- 44 g vs 1,030 +/- 77, 1,380 +/- 1,144 +/- 80 g; means +/- SE), respectively. Minimum fiber diameters in the semitendinosus muscle were larger in obese, lean and Ossabaw fetuses than in Yorkshire and crossbred fetuses (12.9 +/- .3, 12.5 +/- .2 and 11.8 +/- .2 micron vs 10.2 +/- .2 and 11.1 +/- .8 micron), respectively. Histochemical analysis for NADH-tetrazoleum reductase (NADH-TR) and esterase activities indicated no fiber type differentiation and no strain differences. Fiber type differentiation was obvious with acid ATPase histochemistry in muscles from all fetuses. The white portion of the semitendinosus from Ossabaw, obese and lean fetuses had many fibers that contained no histochemically detectable lipid (oil red O staining). The unstained fibers (oil red O) were always the most peripherally located fibers in a fasciculi. In some instances, 50% of the fibers in a fasciculi were not stained for lipid. All the fibers in the red portion of muscle from Ossabaw, obese and lean fetuses contained lipid. All the fibers in the red and white portions of muscles from crossbred and Yorkshire fetuses contained lipid. Muscles from young (1 to 2 d old) Ossabaw, Yorkshire and crossbred pigs were also histochemically analyzed. Analysis for NADH-TR, esterase and alkaline phosphatase (capillary staining) activities indicated no fiber type differentiation and no strain differences. As in the fetuses, the white portion of muscle from Ossabaw pigs had many fibers with no lipid (oil red O). Lipid was present in all fibers in the deep portions of muscle from Ossabaws and in all fibers in both portions of muscle from crossbred and Yorkshire pigs. These results indicate that when lipid staining is used as the criterion, fiber type differentiation is evident in muscle from fetuses and young pigs from strains not genetically selected for muscling (Ossabaw, obese and lean strains). Furthermore, fiber type differentiation is not evident in muscle from strains of pigs genetically selected for greater muscling (crossbred and Yorkshires).

Animals↗

Essential and separable roles for Syndecan-3 and Syndecan-4 in skeletal muscle development and regeneration.

Syndecan-3 and syndecan-4 function as coreceptors for tyrosine kinases and in cell adhesion. Syndecan-3(-/-) mice exhibit a novel form of muscular dystrophy characterized by impaired locomotion, fibrosis, and hyperplasia of myonuclei and satellite cells. Explanted syndecan-3(-/-) satellite cells mislocalize MyoD, differentiate aberrantly, and exhibit a general increase in overall tyrosine phosphorylation. Following induced regeneration, the hyperplastic phenotype is recapitulated. While there are fewer apparent defects in syndecan-4(-/-) muscle, explanted satellite cells are deficient in activation, proliferation, MyoD expression, myotube fusion, and differentiation. Further, syndecan-4(-/-) satellite cells fail to reconstitute damaged muscle, suggesting a unique requirement for syndecan-4 in satellite cell function.

Animals↗

Steroid control of neuron and muscle development during the metamorphosis of an insect.

Insect metamorphosis is controlled by a small ensemble of developmental hormones including a class of steroids--the ecdysteroids. In the tobacco hornworm, Manduca sexta, the progression from the larval to pupal to adult stages is controlled by the relative blood titers of ecdysteroids and juvenile hormone (JH). The cellular events in the nervous and muscular systems which accompany metamorphosis resemble those of embryonic development, but they occur in an animal which is larger and experimentally more tractable than an embryo. In this paper we review the role of ecdysteroids in directing the metamorphosis of the nervous and muscular systems in Manduca, and how JH modifies the cellular responses to the steroids. In particular, we describe how these hormones control muscle degeneration, changes in the structure and function of identified neurons, and programmed neuron death. One general finding is that interactions between cells (e.g., neurons and their target muscles) are not involved in their hormonal responses, but rather the hormones act independently and in parallel at the different sites. Another key finding is that the critical periods and hormonal requirements for the commitment to a particular differentiative pathway, and the phenotypic expression of that pathway, can differ, and are therefore experimentally separable. Finally, we find that the significance of a hormonal signal (e.g., a rise in blood ecdysteroids) is interpreted differently depending upon the previous history of hormone exposure of a neuron or muscle. This progressive change in the interpretation of hormonal signals is a major mechanism by which a limited number of hormones can orchestrate a complicated phenomenon such as metamorphosis.

Aging↗

Transcriptional control of muscle development by myocyte enhancer factor-2 (MEF2) proteins.

Metazoans contain multiple types of muscle cells that share several common properties, including contractility, excitability, and expression of overlapping sets of muscle structural genes that mediate these functions. Recent biochemical and genetic studies have demonstrated that members of the myocyte enhancer factor-2 (MEF2) family of MADS (MCM1, agamous, deficiens, serum response factor)-box transcription factors play multiple roles in muscle cells to control myogenesis and morphogenesis. Like other MADS-box proteins, MEF2 proteins act combinatorially through protein-protein interactions with other transcription factors to control specific sets of target genes. Genetic studies in Drosophila have also begun to reveal the upstream elements of myogenic regulatory hierarchies that control MEF2 expression during development of skeletal, cardiac, and visceral muscle lineages. Paradoxically, MEF2 factors also regulate cell proliferation by functioning as endpoints for a variety of growth factor-regulated intracellular signaling pathways that are antagonistic to muscle differentiation. We discuss the diverse functions of this family of transcription factors, the ways in which they are regulated, and their mechanisms of action.

Animals↗

Effects of chronic heat exposure and protein intake on growth performance, nitrogen retention and muscle development in broiler chickens.

The respective effects of ambient temperature, dietary crude protein and feed intake were investigated in finishing chickens and the consequence of protein supplementation under high temperature conditions was analysed in particular. Heat-related reduction in growth was associated with decreased nitrogen retention (-30 or -35% according to the diet), which could not be explained by the observed lower feed intake alone. Tissue samples performed in 5- to 6-week-old chicks showed varying effects of heat according to the muscles studied: at 32 degrees C, the proportion of Pectoralis major muscle (in percentage of body weight) appeared slightly reduced (reduction lower than 10%), whereas the proportion of two leg muscles were increased (+10 to +15% for the Sartorius muscle; +5% for the gastrocnemius muscle). At 32 degrees C, providing a high protein diet significantly (P < 0.05) increased weight gain and feed efficiency, and slightly improved whole body protein deposition.

Animal Nutritional Physiological Phenomena↗