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At least 1,423 records · Page 79Linked to original sources
PubMed1997

Absence of MEF2 binding to the A/T-rich element in the muscle creatine kinase (MCK) enhancer correlates with lack of early expression of the MCK gene in embryonic mammalian muscle.

During skeletal muscle development, different types of muscle fibers are generated, which express different combinations of muscle-specific gene products. For example, the muscle creatine kinase gene (MCK) is highly expressed in fetal but not embryonic myotubes. We performed transient transfections of CAT reporter constructs, driven by the MCK promoter with variable lengths of 5'-flanking sequence, into primary cultures of embryonic and fetal muscle cells. Reporter activity was observed in fetal but not embryonic muscle cells. We assayed the ability of nuclear extracts prepared from embryonic and fetal muscle and C2C12 myotubes to bind specific regulatory elements in the MCK enhancer. The profile of DNA/protein complexes resulting from electrophoretic mobility shift assays was qualitatively the same with all extracts used when the oligonucleotide probes represented the MCK-E-box, MHox site, CArG-box, and AP2 site. In contrast, no binding activity to the MEF2 site was observed with embryonic nuclear extract. Interestingly, MEF2 mRNAs and proteins were detected in both fetal and embryonic muscle, with the exception of the MEF2D1b isoform, which is restricted to fetal muscle. Furthermore, we found that protein phosphatase inhibitors included in the preparation of embryonic nuclear extracts or added to the medium of transfected embryonic myotubes can restore MEF2 DNA binding activity, as well as reporter activity driven by the MCK promoter and partial transcriptional activation of the endogenous MCK gene. We propose that phosphorylation of MEF2 regulates its activity and represents an important aspect of the mechanism controlling stage-specific transcription during skeletal myogenesis.

Alkaline Phosphatase↗
PubMed1993

In vivo observations of pre- and postsynaptic changes during the transition from multiple to single innervation at developing neuromuscular junctions.

Synaptic rearrangements in developing muscle were studied by visualizing individual neuromuscular junctions in the sternomastoid muscle of living neonatal mice as they underwent the transition from multiple to single innervation. Vital staining of ACh receptors (AChRs) with rhodamine-conjugated alpha-bungarotoxin showed that while junctions were still multiply innervated (usually by two motor axons), regions of the postsynaptic membrane within each junction became depleted of receptors. Usually, several small postsynaptic areas lost AChRs in succession. In these areas, AChRs already in the membrane rapidly disappeared compared to a low level of receptor turnover elsewhere in the junction. Moreover, there was no evidence of new AChRs being inserted into these areas. Within each postsynaptic area undergoing AChR depletion, the intensity of receptor staining decreased gradually over 1-2 d. In some junctions, it appeared that AChRs were migrating away from areas being depleted of receptors. The depletion of AChRs from some sites in combination with the spreading apart of the entire receptor-rich area due to muscle fiber growth accounts for the transformation from plaque-like to branched receptor distributions at developing neuromuscular junctions. Vital staining of presynaptic motor nerve terminals at junctions whose postsynaptic AChRs were also stained showed that motor nerve terminals were lost from the same areas that were depleted of receptors postsynaptically. Postsynaptic areas began to be depleted of AChRs before there was any obvious loss of membrane or intracellular staining in the overlying nerve terminal. Only when a single innervating axon remained at a junction did loss of motor nerve terminals and underlying AChRs largely cease. That former synaptic areas could at later times be identified as uninnervated regions within a junction indicates that synapse elimination during development leaves an indelible mark on synaptic structure. These observations suggest that the withdrawal of a motor axon from a neuromuscular junction occurs as a consequence of the stepwise elimination of all of its synapses with that muscle fiber. These results also suggest that an important aspect of synaptic competition leading to axon withdrawal is the precocious loss of AChRs beneath the nerve terminals of the axon that will be eliminated. A similar early loss of AChRs beneath one axon's synapses has been shown to occur during synapse elimination in reinnervated adult muscle (Rich and Lichtman, 1989a).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1999

MyoR: a muscle-restricted basic helix-loop-helix transcription factor that antagonizes the actions of MyoD.

Skeletal muscle development is controlled by a family of muscle-specific basic helix-loop-helix (bHLH) transcription factors that activate muscle genes by binding E-boxes (CANNTG) as heterodimers with ubiquitous bHLH proteins, called E proteins. Myogenic bHLH factors are expressed in proliferating undifferentiated myoblasts, but they do not initiate myogenesis until myoblasts exit the cell cycle. We describe a bHLH protein, MyoR (for myogenic repressor), that is expressed in undifferentiated myoblasts in culture and is down-regulated during differentiation. MyoR is also expressed specifically in the skeletal muscle lineage between days 10.5 and 16.5 of mouse embryogenesis and down-regulated thereafter during the period of secondary myogenesis. MyoR forms heterodimers with E proteins that bind the same DNA sequence as myogenic bHLH/E protein heterodimers, but MyoR acts as a potent transcriptional repressor that blocks myogenesis and activation of E-box-dependent muscle genes. These results suggest a role for MyoR as a lineage-restricted transcriptional repressor of the muscle differentiation program.

Amino Acid Sequence↗
PubMed1998

p27Kip1 is expressed transiently in developing myotomes and enhances myogenesis.

Vertebrate skeletal muscle development is characterized by tight coupling of muscle differentiation with cell cycle arrest in G1/G0. Key regulators of G1 progression are the G1 cyclin-dependent kinases, their positive regulators, the G1 cyclins, and their negative regulators, the cyclin-dependent kinase inhibitors (CDIs). Here we show that p27Kip1 protein, a G1 CDI, is expressed in a prominent but transient wave in the developing myotomes of the mouse embryo. We relate its expression to expression of MyoD and myogenin proteins, which are determination and differentiation class myogenic regulatory factors, respectively. Functional assays showed that ectopic p27 expression can powerfully enhance the efficiency of MyoD-initiated muscle differentiation in cell culture. When considered together with the myotomal expression patterns of p18, p21, and p57, these results suggest a model in which p27 acts as a "trigger" CDI while myoblasts are exiting the cell cycle and initiating differentiation. At later times, when p27 protein has been down-regulated, it is proposed that accumulation of p18, p21, and p57 maintain the differentiated myocytes in a postmitotic state.

Animals↗
PubMed2003

Extracellular matrix protein expression during mouse detrusor development.

BACKGROUND/PURPOSE: Extracellular matrix proteins are implicated in regulating cell proliferation and differentiation. The authors systematically analysed the expression of elastin; collagen types I, III, IV; laminin; and fibronectin during mouse detrusor muscle development, a period during which downregulation of detrusor proliferation and increasing smooth muscle differentiation is known to occur. METHODS: Embryonic days 14 (E14) and 18 (E18), and postnatal day 1 (D1) and week 6 (6wk) were examined, a period spanning the inception of the bladder to postnatal maturity. Immunohistochemistry of whole bladders was used to immunolocalise protein expression, and Western blot of dissected detrusor layers was used to semiquantify soluble protein expression. RESULTS: All proteins were detected at all 4 stages. Statistically significant increases were documented for elastin (E14 to 6wk), collagen type I (E18 to 6wk), collagen type III (D1 to 6wk) and laminin (E14 to 6wk). Fibronectin levels were relatively high up to D1, after which levels declined significantly. Collagen type IV levels decreased significantly (E18 to 6wk). CONCLUSIONS: The authors postulate that changing levels of laminin and fibronectin have opposing effects on the transition from proliferating primitive mesenchymal cells to differentiated detrusor muscle. Furthermore, changes in collagen type III and elastin may be important for bladder compliance.

Animals↗
PubMed1986

Effects of skeletal change on muscle pattern formation.

The skeletal influence on muscle development was investigated taking an experimental and comparative approach. Chick hindlimbs of HH stage 23 were operated in order to induce the development of an enlarged, elongated fibula - similar to the condition in bird ancestors. The skeletal change resulted in a series of secondary alterations in the later-forming zeugopod muscles. By comparing the results to the zeugopod musculature in other birds and in reptiles it could be shown that changes did not occur at random but resembled the patterns of interspecific variation and ancestral arrangement. It is concluded that skeletal elements influence muscle morphogenesis during a certain period of development. A classification of four phases in muscle development is presented: formation of the premuscular masses; individuation of separate muscles; final shaping and insertion; development maintenance and growth. The factors acting on each level are discussed and it is suggested that skeletal influence becomes effective in phase 3. The results also emphasize the role of development in evolution. The experimental reestablishment of an ancestral epigenetic condition within a developing organ system resulted in ancestral features of subsequently forming characters. This suggests that modification of epigenetic control of gene expression may be an important mechanism in evolutionary change.

Alligators and Crocodiles↗
PubMed1995

The effect of partial denervation of developing rats fast muscles on their motor unit properties.

1. The effects of partial denervation on motor units of the fast twitch extensor digitorum longus (EDL) muscle of the rat were studied. 2. Partial denervation was performed by surgically removing 2-4 mm of the L4 ventral ramus in 3- and 18-day-old Wistar rats. Two to three months later, EMG activity, contractile properties and muscle fibre types were analysed. 3. After partial denervation the EDL muscle became significantly more active, particularly in the animals operated on at 3 days. The amount of activity during periods of rest was up to 4 times that of the control EDL muscle. 4. The maximum tetanic tension developed by the EDL muscles 2 months after partial denervation at 3 days was only 11 +/- 1.01% (S.E.M., n = 18) of the control. In animals operated on at 18 days this value was larger, i.e. 44 +/- 3.46% (S.E.M., n = 12). The low force output of animals operated on at 3 days was also reflected in the low mean motor unit (MU) force output which was only 69 +/- 5.82% (S.E.M., n = 17) of the contralateral control muscle. In contrast the force generated by MUs of rats operated on at 18 days was larger than that of control muscles, i.e. 151 +/- 13.05% (S.E.M., n = 11). The number of MUs was 6 +/- 0.32 (S.E.M., n = 19) in rats operated on at 3 days and 12 +/- 0.83 (S.E.M., n = 14) in rats operated on at 18 days. 5. The speed of contraction decreased and the resistance to fatigue increased. These changes were greater in animals operated on at 3 days. The proportion of muscle fibres reacting with antibody against slow myosin showed a significant increase, especially in the group of animals operated on at 3 days.

Aging↗
PubMed1989

Cellular insertion of primary and secondary myotubes in embryonic rat muscles.

Mammalian muscles develop from two populations of myotubes; primary myotubes appear first and are few in number; secondary myotubes appear later and form most of the muscle fibres. We have made an ultrastructural study to investigate how primary and secondary myotubes in embryonic rat muscles transmit tension during the period of their development. Primary myotubes extend from end to end of the muscle from the earliest times, and attach directly to the tendon. In contrast, newly formed secondary myotubes are short cells which insert solely into the primary myotubes by a series of complex interdigitating folds along which adhering junctions occur. As the secondary myotubes lengthen and mature, their insertion is progressively transferred from the primary myotube to the tendon proper. We suggest that this variable insertion of immature secondary myotubes, combined with complex patterns of innervation and electrical coupling in developing muscle, makes it difficult to predict the overall contribution of secondary myotubes to muscle tension development. This work extends other studies showing the unique relationship between a primary myotube and its associated secondary myotubes, indicating that these may constitute a developmental compartment.

Animals↗
PubMed1991

Nutritional ergogenic aids: chromium, exercise, and muscle mass.

Athletes who want to develop muscle mass have sought various ways to reach this goal. We are all too familiar with the abuse of anabolic steroids and growth hormone. Given the concern for such abuses, athletes and coaches are seeking new and safer means to achieve the same end. Within the last couple of years, advertisements for chromium supplements have been prominently displayed in body-building and strength-training magazines. These supplements are purported to be a safe alternative to anabolic steroids and are said to promote an increase in muscle mass. This brief review will focus on the theoretical basis for believing that chromium supplements will increase muscle mass, and on the current research regarding the relationship of chromium and exercise.

Chromium↗
PubMed2004

Morphogenesis of parrot jaw muscles: understanding the development of an evolutionary novelty.

Parrots have developed novel head structures in their evolutionary history. The appearance of two new muscles for strong jaw adduction is especially fascinating in developmental and evolutionary contexts. However, jaw muscle development of parrots has not been described, despite its uniqueness. This report first presents the normal developmental stages of the cockatiel (Nymphicus hollandicus), comparable to that of the chick. Next, the peculiar skeletal myogenesis in the first visceral arch of parrots is described, mainly focusing on the development of two new jaw muscles. One of the parrot-specific muscles, M. ethmomandibularis, was initially detected at Nymphicus Stage 28 (N28) as the rostral budding of M. pterygoideus. After N32, the muscle significantly elongates rostrodorsally toward the interorbital septum, following a course lateral to the palatine bone. Another parrot-specific muscle, M. pseudomasseter, was first recognized at N36. The muscle branches off from the posteromedial M. adductor mandibulae externus and grows in a dorsolateral direction, almost covering the lateral surface of the jugal bar. The upper tip of the muscle is accompanied by condensed mesenchyme, which seems to be derived from cephalic neural crest cells.

Animals↗
PubMed1998

In ovo administration of recombinant human insulin-like growth factor-I alters postnatal growth and development of the broiler chicken.

Two experiments assessed the efficacy of in ovo administration of insulin-like growth factor-I (IGF-I) to enhance skeletal muscle development and improve feed efficiency of broilers. Hatching eggs were divided into three groups: uninjected control, vehicle-injected control, and recombinant human (rh) IGF-I (100 ng per embryo). Eggs in Experiment 1 were injected on Day 1, 4, or one of Day 7 through 18 of incubation. Growth rates for Days 1 and 4 resulted in the greatest response to treatment (P < 0.01, P < 0.06 respectively). Based on these results, Experiment 2 focused on Days 1 to 4 of incubation. Results from Experiment 2 showed that there was no significant difference in hatchability among control and rh IGF-I treatment groups. Injection on Day 3 resulted in the greatest response for increased live (P < 0.035) and leg (P < 0.02) weights in both sexes. Feed efficiencies of all rh IGF-I groups were significantly (P < 0.01) improved for the first 3 wk. In ovo administration of rh IGF-I on Day 3 increased feed efficiency (6.65%; P < 0.009) in pens of mixed-sex broilers. In addition, live weights (12.3%; P < 0.002), leg weights (11.7%; P < 0.01), breast weights (9.9%; P < 0.04), and heart weights (11.4%; P < 0.02) were increased in males. These results demonstrate that in ovo administration of rh IGF-I alters feed efficiency, growth, and tissue development. This finding lends itself to significant improvements in broiler production efficiency and profitability.

Animal Nutritional Physiological Phenomena↗
PubMed1999

Expression of two ATP-gated ion channels, P2X5 and P2X6, in developing chick skeletal muscle.

Physiological and pharmacological studies have shown that ATP has potent effects on developing chick skeletal muscle. These effects have previously been shown to be developmentally regulated, and the responses were characteristic of activation of the P2X ligand-gated ion-channel family of ATP receptors. Here, using immunohistochemistry, we describe the expression patterns of two members of the P2X receptor family, P2X5 and P2X6, during development of skeletal muscle in the chick embryo. These receptors were first expressed at early stages of skeletal muscle development, and expression disappeared immediately before the stage at which fusion of myoblasts to form myotubes occurs. P2X5 was also demonstrated in nerves supplying developing skeletal muscle, in some dorsal root ganglion cells, and in dorsal and ventral spinal cord. No expression of the other five members of the P2X family were demonstrated in developing skeletal muscle.

Amino Acid Sequence↗
PubMed1998

Skeletal muscle fibre types: detection methods and embryonic determinants.

Muscle fibres used to be simply classified as either type I, IIa or IIb. Advances in molecular and histological techniques have, however, lead to the realisation that the phenotypes of muscles are more varied than this. An additional fibre type (IIX/IID) has been discovered, fibres with intermediate fibre types have been described and there is accumulating evidence that the fibres types described from the study of limb muscles are not necessarily applicable to other skeletal muscles, such as the jaw and extra-ocular muscles. Further to this has been the discovery that diversity occurs at all stages of muscle development. There are subpopulations of myoblasts and myotubes as well as various types of muscle fibres. The relationships between the different stages of development is still under study. However, it is clear that each stage of muscle development is influenced to a certain degree by prior events. Consequently, the characteristics of mature fibres reflect both their developmental origins and influences from the adult environment, such as their patterns of muscle activation.

Adenosine Triphosphatases↗
PubMed1998

Polyneural innervation in the psoas muscle of the developing rat.

Polyneural innervation was studied in the psoas muscle in developing rats from P4 till P25 and at adult age, with the combined silver-acetylcholinesterase technique. Nerve endings were counted, and end-plates were measured. These data were compared with such data in the human. The end of polyneural innervation in the rat (around P20) and in the human (around 12 weeks postterm age) in both cases coincides with a transformation in motor behavior and postural control. The rat's psoas muscle at early stages is less heavily innervated than this muscle in the human. Up to three axons per motor end-plate were counted at P4, but in the human up to five axons at 25 weeks of post menstrual age. This difference might be related to the lower percentage of type I muscle fibers in the rat.

Animals↗
PubMed1988

Regulation of transcript encoding the 43K subsynaptic protein during development and after denervation.

The postsynaptic membrane of vertebrate neuromuscular synapses is enriched in the four subunits of the acetylcholine receptor (AChR) and in a peripheral membrane protein of Mr = 43 x 10(3) (43K). Although AChRs are virtually restricted to the postsynaptic membrane of innervated adult muscle, developing and denervated adult muscle contain AChRs at nonsynaptic regions. These nonsynaptic AChRs accumulate because the level of mRNA encoding AChR subunits increases in response to a loss of muscle cell electrical activity. We have determined the level of mRNA encoding the 43K subsynaptic protein in developing muscle and in innervated and denervated adult muscle. We isolated a cDNA that encodes the entire protein-coding region of the 43K subsynaptic protein from Torpedo electric organ and used this cDNA to isolate a cDNA that encodes the 43K subsynaptic protein from Xenopus laevis. We used the Xenopus cDNA to measure the level of transcript encoding the 43K protein in embryonic muscle and in innervated and denervated adult muscle by RNase protection. The level of transcript encoding the 43K protein is low in innervated adult muscle and increases 25- to 30-fold after denervation. The level of transcript encoding the alpha subunit of the AChR increases to a similar extent after denervation. Moreover, during development, transcripts encoding the 43K protein and the alpha subunit are expressed initially at late gastrula and are present in similar quantities in embryonic muscle. These results demonstrate that transcripts encoding the 43K protein and AChR subunits appear coordinately during embryonic development and that the level of mRNA encoding the 43K protein is regulated by denervation.

Amino Acid Sequence↗
PubMed1985

Variability in limb malformations and possible significance in the pathogenesis of an inherited congenital neuromuscular disease of Charolais cattle (syndrome of arthrogryposis and palatoschisis).

Limb abnormalities in 30 calves with an inherited congenital neuromuscular disorder known as syndrome of arthrogryposis and palatoschisis were classified according to the range of severity of joint deformity in either flexion or extension, and restricted joint movement. Joint movement was variably affected; it was either normal, lax, restricted in the range of mobility, or occasionally, fixed. The characteristic findings were: bilateral hyperextension of the hind fetlock, flexion deformity of the forelimb that particularly involved the fetlock and the carpus, with restricted articular movement and complete rigidity in some cases. One-third of calves also had medial deviation of the forelimb due to angular deformity of articular surfaces in the carpus. All nine live calves were floppy due to marked generalized muscular hypotonia. Birth weight of deformed calves was reduced. In some calves muscle development was impaired as judged by muscle weight, and histological examination. In some calves the gross appearance, muscle weight and histological examination revealed no abnormal development and indicated that the effects on skeletal muscle were secondary. No lesions were found in the spinal cord of 23 of 24 calves examined histologically. The remaining calf had a localized cavitation in the dorsal white matter at T2-3. Based on the observations in calves in this study it is proposed that both primary and secondary factors contribute to the phenotypic expression of this congenital deformity. The primary lesion is considered to be a neurogenic abnormality of differentiation in the central nervous system. Cytogenetic analysis of 16 carrier cows and two deformed calves showed normal karyotypes. Serology for Akabane virus in 16 carrier cows was negative.

Abnormalities, Multiple↗