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PubMed1995

The human troponin I slow promoter directs slow fiber-specific expression in transgenic mice.

Troponin I (TnI) is a muscle-specific protein involved in the calcium-mediated contraction of striated muscle. Three TnI isoforms have been identified, each encoded by a separate gene and expressed in specific striated muscles in the adult. The slow isoform gene (TnIs) is transcriptionally regulated during skeletal muscle development such that its expression in the adult is restricted to muscle fibers innervated by a slow nerve. To delineate regions of this gene that are responsive to information imparted by the slow nerve, we generated transgenic mice carrying -4,200 to +12 bp of the human TnIs gene linked to the bacterial chloramphenicol acetyltransferase (CAT) coding region. By Northern blot analysis, we detected transgene transcripts only in muscles containing slow-twitch fibers. CAT histochemical analysis revealed that expression of the transgene is restricted solely to slow-twitch fibers as characterized by type I myosin heavy-chain (MyHC) expression. Using regeneration as a model for neural influenced expression, we show that this gene construct also contains sequences necessary to respond to cues from the central nervous system.

Animals↗
PubMed2006

Congenital myotonic dystrophy: variability in muscle involvement and histopathological process.

In order to understand the involvement of specific muscles in congenital myotonic dystrophy type 1 (DM1), we studied the clinical manifestations, and the genetic effects on various tissues in 2 siblings with congenital DM1. The distal leg muscles were more severely involved than the thigh muscles, as seen in the skeletal muscle magnetic resonance imaging. Molecular genetic analysis of the myotonic dystrophy type 1 protein kinase showed an elongation of the CTG triplet repeats between 850 and 1400 in the leukocytes, skin, fat, tendon, and muscles. Muscle biopsies showed a significant difference in the fiber type distribution between these two congenital DM1 patients. One revealed a prominent involvement of the tibialis anterior muscle with a predominance of type 1 fibers, similar to those muscle fiber distributions in older congenital or classic DM1 patients, suggesting a neurotrophic influence during muscle development. Another revealed a predominance of type 2 fibers in all muscle specimens, and dystrophic changes were observed in the peroneus longus muscle indicating a delayed differentiation or maturation of muscle fibers. We conclude that despite nearly the same number of CTG repeats in the leukocytes, highly individual variability of muscle differentiation may occur at teenagers of congenital DM1 in addition to different pathological findings in various skeletal muscles of patients with congenital DM1.

Adolescent↗
PubMed1994

Regenerating muscle fibers induce directional sprouting from nearby nerve terminals: studies in living mice.

The principal aim of this work was to better understand how regenerating muscle fibers become innervated in adult animals. To induce muscle regeneration, individual identified muscle fibers in a mouse were damaged with a laser focused through a microscope. The muscle fiber that degenerated and the muscle fiber that was formed in its place were followed by viewing the same site repeatedly over a period of 2 d to 40 weeks. Commonly, the nerve terminal innervating the irradiated muscle fiber partially retracted during muscle fiber degeneration, and then sprouted to innervate the regenerating muscle fiber at the same site it had previously innervated the muscle fiber that was damaged. During the early phase of muscle regeneration we also observed sprouts originating from nerve terminals on adjacent muscle fibers. The new nerve growth was a response to the regenerating muscle fiber rather than to the degenerated fiber it replaced because repeated damage of the same site every 2-3 d over a 10 d period (to prevent regeneration) did not cause any sprouting. The direction of the sprouts on adjacent muscle fibers showed a bias toward the regenerating muscle fiber, although they avoided the region occupied by the original nerve terminal. Forty percent of the sprouts managed to reach the regenerated fiber. Nonetheless, by 11 d after muscle fiber damage, all sprouts had regressed, leaving the new fiber innervated by the same motor axon that innervated the fiber that was damaged. On the other hand, when the overlying nerve terminal as well as the muscle fiber was damaged, the sprouts from nearby muscle fibers were both more numerous and more stable, and in five cases we observed two or more new synaptic junctions on the regenerating fiber originating from different axons. In one case we witnessed a protracted competition between the original motor axon as it sprouted back and the sprouts from nearby junctions for sole innervation of the regenerate. Ultimately, the surviving sprouts myelinated and became the permanent and exclusive input to the new fiber. These results indicate that regenerating muscle fibers emit a signal that induces directional sprouting from nearby undamaged nerve terminals. Reinnervation of the regenerating muscle fiber by one axon apparently prevents the maintenance of such neurites. Because the process of muscle regeneration shares many features in common with myogenesis during embryonic development, it is likely that developing muscle fibers present an analogous stimulus to ingrowing motor axons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

The dependence of motoneurons on their target muscle during postnatal development of the mouse.

Motoneurons seem to require contact with their target muscle even after embryogenesis is complete, but the consequences of target-deprivation during postnatal development are poorly understood. To examine the fate of motoneurons separated from their targets postnatally, we labeled the motoneurons that innervate the biceps brachii muscle with the retrograde tracer Fluorogold and then separated them from their muscle by amputating the forelimb. Fluorogold was subsequently found within motoneurons, as well as within much smaller cells that were identified as microglia. The number of labeled microglial cells steadily increased with time following limb amputation, while the number of labeled motoneurons declined. The magnitude of this response depended on the age of the animal: the younger the animal at the time of the amputation, the greater the number of labeled microglia and the more extensive the neuronal loss. To ensure that the response to amputation was caused by target deprivation, rather than by the injury itself, the nerve to the biceps muscle was cut or crushed. In this way, axons were transected but target access was only temporarily denied. After the nerve was cut, motoneurons began to reinnervate the muscle within 3 weeks but, just as after amputation, the spinal cord subsequently contained labeled microglia and a reduced number of motoneurons. In contrast, after nerve crush, reinnervation began within 4 d and there was no evidence of motoneuron death. Our results demonstrate that target-deprivation causes motoneurons to be lost in an age- and time-dependent manner, and indicate a critical period after axotomy during which motoneurons must reinnervate their target in order to survive. Further, we provide evidence that microglial cells may phagocytose dying motoneurons. The approach we used would provide a convenient assay for testing candidate motoneuron growth factors in animals where in vivo studies of the embryo are difficult.

Amputation, Surgical↗
PubMed2003

Calcium/calmodulin-dependent protein kinase activates serum response factor transcription activity by its dissociation from histone deacetylase, HDAC4. Implications in cardiac muscle gene regulation during hypertrophy.

Serum response factor (SRF) plays a pivotal role in cardiac myocyte development, muscle gene transcription, and hypertrophy. Previously, elevation of intracellular levels of Ca2+ was shown to activate SRF function without involving the Ets family of tertiary complex factors through an unknown regulatory mechanism. Here, we tested the hypothesis that the chromatin remodeling enzymes of class II histone deacetylases (HDAC4) regulate SRF activity in a Ca2+-sensitive manner. Expression of HDAC4 profoundly repressed SRF-mediated transcription in both muscle and nonmuscle cells. Protein interaction studies demonstrated physical association of HDAC4 with SRF in living cells. The SRF/HDAC4 co-association was disrupted by treatment of cells with hypertrophic agonists such as angiotensin-II and a Ca2+ ionophore, ionomycin. Furthermore, activation of Ca2+/calmodulin-dependent protein kinase (CaMK)-IV prevented SRF/HDAC4 interaction and derepressed SRF-dependent transcription activity. The SRF.HDAC4 complex was localized to the cell nucleus, and the activated CaMK-IV disrupted HDAC4/SRF association, leading to export of HDAC4 from the nucleus and stimulation of SRF transcription activity. Thus, these results identify SRF as a functional interacting target of HDAC4 and define a novel tertiary complex factor-independent mechanism for SRF activation by Ca2+/CaMK-mediated signaling.

Animals↗
PubMed1980

Electron microscopic examination of lead treated L6 skeletal muscle line cells in culture.

A study has been made of the effects of lead on developing muscle using a cell culture system. When the L6 clonal cell line was treated with lead acetate in culture during the first or second day after plating (but not at later times) fusion of cells to form skeletal muscle straps was inhibited. This inhibition was not due to a general toxic effect of lead on the cells since cell division continued at a normal rate during the first 10 days of culture after lead addition. When cells were examined ultrastructurally using stereology, the only apparent effect of lead was a change in mitochondrial size and configuration. Five times as many partially condensed mitochondria were seen in lead treated cells, and mitochondrial size was also significantly increased. Lead appears to effect a very early event in cell fusion since gap junction formation (a necessary event in fusion) and some synthesis of myofibrils occur even in the presence of lead.

Cell Fusion↗
PubMedDate not supplied

[Ontogenetic divergence in the phytoparasitic nematodes Macroposthonia nainitalensis and M. tenuiannulata (Criconematidae, Tylenchia)].

Promorphogenesis, egg cleavage, and gastrulation proceed in Macroposthonia nainitalensis similarly to other phytonematodes of the subclass Tylenchia. Before the onset of gastrulation, the greatest similarity was observed in a descendant of the micromere 2b, which separates macromeres of the third division. Deviations from the general line of development started in this species during embryonal organogenesis with the formation of an external epithelium with a special rough surface layer, which was absent in the embryos of other phytonematodes. In addition, during this period of acceleration, the digestive system developed, while peristaltic changes in body shape appeared at the tadpole stage. Later, somatic muscle development was enhanced in the first instar larvae of M. nainitalensis, while in the second instar larvae of Macroposthonia spp. somatic muscle cells were located at an acute angle to the longitudinal body axis. In addition, denticles--microchaetae appeared in the second to fifth instar larvae of these nematodes. All these features, which have not been observed in other phytonematodes of the subclass Tylenchia, help the peristaltic crawling of Macroposthonia spp. In contrast to other Tylenchia, the musculocutaneous sac did not develop in Macroposthonia spp. However, there are similarities in the development of the digestive and genital systems.

Animals↗
PubMed1987

Distribution of fiber types in embryonic chick limb muscles innervated by foreign motoneurons.

The differentiation of distinct myotube fiber types in chick limb muscle development is coincident with innervation. The role of motoneurons in influencing fiber type differentiation was analyzed by causing chick hind limb muscles to be innervated by inappropriate motoneurons and then examining experimental muscles for changes in the distribution of myosin ATPase fiber types. Motoneuron innervation of limb muscles was altered by performing either limb shifts, limb reversals, or large spinal cord reversals on early neural tube or limb bud stage chick embryos. The distribution of fiber types was then analyzed in muscles from stage 36 (E10) to stage 45 (E20) embryos after processing hind limb sections for myosin ATPase histochemistry. In the majority of experimental muscles examined (267/312), the distribution of myosin ATPase fiber types was unaltered. In the remaining experimental muscles (14%), alterations in the distribution of myosin ATPase fiber types occurred, indicating that in some cases, foreign innervation may alter the developmental program of differentiating myotubes. The results suggest that myotubes differentiate myosin ATPase staining characteristics according to an intrinsic program and that these differentiating myotubes are selectively innervated by motoneurons of the appropriate type under most conditions including normal development. Under exceptional circumstances of motoneuron-muscle fiber type mismatch, embryonic motoneurons can alter fiber type expression.

Adenosine Triphosphatases↗
PubMed1994

[The effect of weightlessness on embryonic development of striated muscles in Japanese quail].

In the conditions of gravitationless state, the development of skeletal muscles and myocardium was identical in experimental, synchronous and laboratory control. There were not larger differences between the investigated groups of animals. Myofibrils were in the stage of myofibrillogenesis. They were mostly disarrayed, but they already formed sarcomeres, without marked boundaries between I and A zones. Sarcoplasm contained large amounts of ribosomes and polyribosomes. Mitochondria were intensively splitting, and they contained small numbers of mitochondrial particles. Osmiophilic bodies and granules were detected frequently. Sarcoplasmic reticulum and Golgi apparatus were well developed. Our findings are in agreement with the results published in papers dealing with the embryonal development of striated muscles.

Animals↗
PubMed1993

A new approach of urodele amphibian limb regeneration: study of myosin isoforms and their control by thyroid hormone.

In P. waltlii, an urodele amphibian species which undergoes spontaneous metamorphosis, study of native myosin in pyrophosphate gels at various stages of normal development demonstrates a complete larval to fast myosin isoforms transition, which occurs more precociously in forelimb muscles than in the dorsal and ventral muscles. In the neotenic species A. mexicanum, forelimb muscles development also presents a complete myosin isoforms transition which is in contrast with the partial myosin isoforms transition observed in the dorsal muscle. In metamorphosed or neotenic animals of both species aged 1 year, forelimb regeneration is characterized by a complete transition from larval to fast myosin isoforms, that occurs earlier and more rapidly than in normal forelimb development. When forelimb regeneration is studied in P. waltlii aged 4 years, the adult fast and slow isomyosins are expressed very early in the regeneration process. In experimental hypothyroidian P. waltlii, the larval to fast isoforms transition in regenerating forelimb muscles is slightly delayed. Experimental hyperthyroidism accelerates the disappearance of larval isomyosins in regenerating forelimb muscles, both in P. waltlii and A. mexicanum aged 1 year. This work demonstrates that changes in myosin isoform pattern during forelimb regeneration in adult urodele amphibians are different from changes occurring in the normal forelimb development. They take place without any thyroid hormone influence, as opposed to normal development, and appear to be age-dependent.

Ambystoma↗
PubMed2002

Analysis of the expression pattern of Mysidium columbiae wingless provides evidence for conserved mesodermal and retinal patterning processes among insects and crustaceans.

The Wnt family includes a number of genes, such as wingless ( wg), which encode secreted glycoproteins that function in numerous developmental patterning processes. In order to gain a better understanding of crustacean pattern formation, a wg orthologue was cloned from the malacostracan crustacean Mysidium columbiae(mysid), and the expression pattern of this gene was compared with that of Drosophila wg. Although Drosophila wg is expressed in many developing tissues, such as the ventral neuroectoderm, M. columbiae wg (mcowg)expression is detected within only a subset of these tissues. mcowg is expressed in the dorsal part of each developing segment and within the developing eye, but not within the ventral neuroectoderm. Dorsal wg expression in Drosophila is required for heart and muscle development, and conservation of this dorsal wgexpression pattern suggests that mcowgmay function to pattern these tissues in mysids. Consistent with this, expression of Even-skipped (Eve) protein in heart precursor and muscle cells, which is dependent on Wg signaling in Drosophila, is also conserved in mysids. Within the developing mysid eye, mcowg is expressed in a pattern that is similar to the expression pattern of Drosophila wg in the fly eye disc. In Drosophila,Wg inhibits neural differentiation at the anterior margin of the eye disc and patterns the dorsal/ventral axis of the eye. These data indicate that mcowg may function similarly during mysid eye development. Analysis of mcowgexpression provides molecular evidence suggesting that the processes of heart, muscle, and eye patterning are likely to be conserved among insects and crustaceans.

Amino Acid Sequence↗
PubMed1977

The lipid composition of muscle cells during development.

Developmental changes in the phospholipid, cholesterol, and fatty acid composition of chicken pectoralis muscle cells were analyzed during development in vivo and in tissue culture. The phospholipid composition of muscle cells showed only minor changes during in vivo or in vitro development but there were significant alterations in fatty acid composition. During in vivo development between the 12th and 22nd days the concentration of palmitate and arachidonate decreased with increase in linoleate. In cultured muscle cells the fatty acid composition changes with surprising plasticity depending on the fatty acid supply. Compensatory changes were observed in the chain length and unsaturation of several fatty acids, aimed presumably at maintaining the physical properties of the lipid phase relatively constant.

Animals↗
PubMed1995

Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud.

Limb muscles develop from cells that migrate from the somites. The signal that induces migration of myogenic precursor cells to the limb emanates from the mesenchyme of the limb bud. Here we report that the c-met-encoded receptor tyrosine kinase is essential for migration of myogenic precursor cells into the limb anlage and for migration into diaphragm and tip of tongue. In c-met homozygous mutant (-/-) mouse embryos, the limb bud and diaphragm are not colonized by myogenic precursor cells and, as a consequence, skeletal muscles of the limb and diaphragm do not form. In contrast, development of the axial skeletal muscles proceeds in the absence of c-met signalling. The specific ligand of the c-met protein, the motility and growth factor scatter factor/hepatocyte growth factor, is expressed in limb mesenchyme and can thus provide the signal for migration which is received by c-met. We have therefore identified a paracrine signalling system that regulates migration of myogenic precursor cells.

Animals↗
PubMed1987

Partial muscle carnitine palmitoyltransferase-A deficiency. Rhabdomyolysis associated with transiently decreased muscle carnitine content after ibuprofen therapy.

After initiation of ibuprofen therapy, a 45-year-old woman developed muscle weakness and tenderness with rhabdomyolysis, culminating in respiratory failure. A muscle biopsy specimen showed a vacuolar myopathy, and markedly decreased muscle carnitine content and carnitine palmitoyltransferase activity. Following recovery, muscle carnitine content was normal but carnitine palmitoyltransferase activity was still abnormally low. The ratio of palmitoyl-coenzyme A plus carnitine to palmitoylcarnitine oxidation by muscle mitochondria isolated from the patient was markedly decreased. We conclude that transiently decreased muscle carnitine content interacted with partial deficiency of carnitine palmitoyltransferase-A to produce rhabdomyolysis and respiratory failure and that ibuprofen may have precipitated the clinical event.

Acyltransferases↗
PubMed1987

Physiological features of the opercularis muscle and their effects on vibration sensitivity in the bullfrog Rana catesbeiana.

The amphibian opercularis muscle connects a movable otic element (the operculum) to the pectoral girdle and can act in reception of ground vibrations. Various physiological parameters of the opercularis muscle of the bullfrog Rana catesbeiana were measured and compared with similar measurements on the iliofibularis muscle of the hindlimb. The opercularis muscle is a very slowly contracting muscle, with a Vmax of 1.81 muscle lengths s-1 compared to a Vmax of 6.24 muscle lengths s-1 for the iliofibularis muscle. The opercularis muscle develops tension slowly, taking about 10 s to attain maximum isometric tension when stimulated at 100 Hz. The muscle can retain high levels of tension for several minutes, and following stimulation has a time to half-relaxation of about 4-6 s. The slow velocity of contraction, slow rate of tension development, fatigue-resistance and slow rate of relaxation of the opercularis muscle support morphological evidence that it consists mostly of tonic muscle fibres. Experiments were also made to examine the effects of muscle tension on reception of ground vibrations as measured by inner ear microphonics. Severing the nerve supplying the opercularis muscle produced slight decreases of no more than 2 dB in responses to vibrations from 25 to 200 Hz. Artificial stimulation of the opercularis muscle after severing the nerve supplying the muscle increased responses to vibration across the entire frequency range. Higher tension levels produced greater increases in responses; at the highest tensions used (about 120 kN m-2) responses were increased by as much as 4.5 dB. The opercularis muscle is therefore specialized for slow but prolonged contractions, and tension is important in its sensory function. A tensed opercularis muscle appears to transmit faithfully motion of the forelimb, produced by vibrations, to the operculum such that the latter moves relative to the inner ear fluids.

Animals↗
PubMed1994

Embryonic chicken gizzard: smooth muscle and non-muscle myosin isoforms.

Antibodies to smooth muscle and non-muscle myosin allow the development of smooth muscle and its capillary system in the embryonic chicken gizzard to be followed by immunofluorescent techniques. Although smooth muscle development proceeds in a serosal to luminal direction, angiogenetic cell clusters develop independently at the luminal side close to the epithelial layer, and the presumptive capillaries invade the developing muscle in a luminal to serosal direction. The smooth muscle and non-muscle myosin heavy chains in this avian system cannot be separated by SDS polyacrylamide gel electrophoresis and do not show isoform specificity in immunoblotting, unlike the system found in mammals. Only two myosin heavy chains with M(r) of 200 and 196 kDa were separable and considerable immunological cross-reactivity was found between the denatured myosin isoform heavy chains.

Animals↗
PubMed1975

An analysis of muscle weight variations in the hindlimbs of Rana esculenta.

Dry weights of 24 muscles of the left and of the right hindlimbs in 63 frogs (Rana esculenta) are determined. By means of factor analysis is calculated which part of the variance in a muscle's weight can be accounted for by common factors and which part by the characteristics of the muscle itself. The main results are: 1. Body size (factor 1) accounts for more than 90% of the variance in all the heavier muscles and more than 64% in the eight lighter muscles. 2. Since only one single common factor is found, no separate groups of highly correlated muscle weights are present in the frog's hindlimb. 3. A decrease in the number of fibers is coupled with an increase in the residual variance of a muscle. 4. Left and right identic muscles follow the same variation-pattern. Two models for muscle development are discussed: 1. A model in which the innervation of the muscle determines the number of fibers. 2. A model in which clumping play an important role.

Animals↗
PubMed2026

Comparative transcriptome analysis reveals ncRNA-mediated regulatory networks associated with muscle crispiness in grass carp.

Non-coding RNAs (ncRNAs) have been demonstrated to be involved in muscle development and to function as key regulators. However, the molecular mechanism underlying muscle crispiness in grass carp (GC) remains poorly understood, and whether these ncRNAs are involved in its regulation is still unknown. In the current investigation, differentially expressed (DE) RNAs (including lncRNAs, circRNAs, miRNAs, and mRNAs) were identified; concomitantly, target genes prediction was conducted, and functional and signaling pathway enrichment analyses were performed. Pathways related to muscle crispiness were identified, and the competitive endogenous RNA (ceRNA) (lncRNA/circRNA-miRNA-mRNA) regulatory network was further constructed. The results showed that a total of 126 DE-lncRNAs, 17 DE-circRNAs, 329 DE-miRNAs, and 442 DE-mRNAs were identified in muscle tissues of both the GC and crisp grass carp (CGC). GO and KEGG enrichment analyses revealed that target genes of DE-ncRNAs were significantly enriched in signaling pathways, including structural constituents of muscle, apoptosis, oxidative phosphorylation, and regulation of actin cytoskeleton, suggesting that these pathways may be involved in muscle texture remodeling. Subsequently, DE-RNAs enriched in related pathways were identified, and a core ceRNA regulation network comprising 3 lncRNAs, 4 circRNAs, 3 miRNAs, and 17 mRNAs was constructed. Additionally, 10 DE-RNAs from randomly selected groups were validated by qRT-PCR. Our findings not only provide scientific evidence elucidating the molecular mechanisms underlying muscle crispiness in GC but also establish a foundation for studying changes in muscle textural qualities across other fish species.

Animals↗