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PubMed2002

A zebrafish unc-45-related gene expressed during muscle development.

We report the isolation and expression pattern of zebrafish unc45r, a gene related to Caenorhabditis elegans unc-45. UNC-45 is a muscle-specific protein thought to interact with myosin and promote the assembly of muscle thick filaments during C. elegans development. Zebrafish Unc45r shares sequence features with C. elegans UNC-45, including three tetratricopeptide repeats and a CRO1/She4p homology domain. unc45r is expressed in mesoderm adjacent to the dorsal midline during late gastrula stages and is coexpressed with muscle specific genes in somitic mesoderm during development of trunk skeletal muscle. unc45r is also expressed in cranial skeletal muscle as well as in cardiac and smooth muscle. The isolation of a muscle-specific unc-45 related gene from zebrafish suggests a common mechanism for muscle filament assembly between vertebrates and invertebrates.

Amino Acid Sequence↗
PubMed1994

Regulation of Pax-3 expression in the dermomyotome and its role in muscle development.

The segmented mesoderm in vertebrates gives rise to a variety of cell types in the embryo including the axial skeleton and muscle. A number of transcription factors containing a paired domain (Pax proteins) are expressed in the segmented mesoderm during embryogenesis. These include Pax-3 and a closely related gene, Pax-7, both of which are expressed in the segmental plate and in the dermomyotome. In this paper, we show that signals from the notochord pattern the expression of Pax-3, Pax-7 and Pax-9 in somites and the subsequent differentiation of cell types that arise from the somitic mesoderm. We directly assess the role of the Pax-3 gene in the differentiation of cell types derived from the dermomyotome by analyzing the development of muscle in splotch mouse embryos which lack a functional Pax-3 gene. A population of Pax-3-expressing cells derived from the dermomyotome that normally migrate into the limb are absent in homozygous splotch embryos and, as a result, limb muscles are lost. No abnormalities were detected in the trunk musculature of splotch embryos indicating that Pax-3 is necessary for the development of the limb but not trunk muscle.

Animals↗
PubMed1981

Skeletal muscle development in the fetal pig after decapitation in utero.

The effect of fetal decapitation on skeletal muscle growth and development in utero was studied in the pig. Pig fetuses were decapitated at 45 days of gestation and the peroneus longus muscle was analyzed at 110 days of gestation. Muscle wet weight, length, minimum fiber diameter, DNA, RNA, protein content, and incidence of muscle fiber nuclei and satellite cell nuclei were determined in the decapitated fetus and in sham-decapitated control fetuses. Decapitation did not significantly influence (p greater than 0.05) any of the traits measured. Muscle and satellite cell ultrastructure was not altered by decapitation. Therefore, an intact brain and hypothalamic-hypophyseal axis are not critical to growth and development of fetal pig skeletal muscle as measured in this study.

Animals↗
PubMed1984

Physiologic and histologic features of muscle development in the hamster.

This study determined to what extent the hind limb muscles of hamsters resemble those of other mammals in undergoing changes in physiologic, morphologic, and histochemical properties as a function of age. Maximal isometric twitch and tetanic responses were evoked in soleus and plantaris muscles of hamsters aged 13 days to 6 months; all experiments were conducted in vivo under sodium pentobarbital anesthesia. In keeping with findings in the cat and rat, both hamster muscles had relatively prolonged twitches in the youngest animals; the twitches became briefer during development, that of plantaris having a minimum mean contraction time of 15.4 +/- 2.4 ms at 20 days and that of soleus, 28.3 +/- 3.5 ms at 46 days. In both muscles there was a subsequent slight prolongation of the twitch. The two muscles had similar masses at 13 and 20 days; thereafter the plantaris became considerably larger and stronger than the soleus and developed more tetanic tension per unit cross-sectional area. In keeping with its briefer contraction, plantaris had a more rapid rate of rise of tetanic tension than soleus and was more susceptible to fatigue; whereas the soleus developed depression of the twitch after a tetanus, the plantaris exhibited potentiation. Histological and histochemical studies showed that the plantaris had significantly more muscle fibers than the soleus and a much greater proportion of type II fibers (91 and 39%, respectively, in 120- to 180-day-old animals). Whereas the type II fibers had similar cross-sectional areas in the two muscles, the type I fibers were significantly smaller in plantaris than in soleus.

Aging↗
PubMed1995

Duels without obvious sense: counteracting inductions involved in body wall muscle development in the Caenorhabditis elegans embryo.

During the first four cleavage rounds of the Caenorhabditis elegans embryo, five somatic founder cells AB, MS, E, C and D are born, which later form the tissues of the embryo. The classical criterion for a cell-autonomous specification of a tissue is the capability of primordial cells to produce this tissue in isolation from the remainder of the embryo. By this criterion, the somatic founder cells MS, C and D develop cell-autonomously. Laser ablation experiments, however, reveal that within the embryonic context these blastomeres form a network of duelling cellular interactions. During normal development, the blastomere D inhibits muscle specification in the MS and the C lineage inhibits muscle specification in the D lineage. These inhibitory interactions are counteracted by two activating inductions. As described before the inhibition of body wall muscle in MS is counteracted by an activating signal from the ABa lineage. Body wall muscle in the D lineage is induced by MS descendants, which suppress an inhibitory activity of the C lineage. The interaction between the D and the MS lineage occurs through the C lineage. An interesting feature of these cell-cell interactions is that they do not serve to discriminate between equivalent cells but are permissive or nonpermissive inductions. No evidence was found that the C-derived body wall muscle also depends on an induction, which suggests that possibly three different pathways coexist in the early embryo to specify body wall muscle, two of which are, in different ways, influenced by cell-cell interactions and a third that is autonomous. This work supplies evidence that cells may acquire transient states during embryogenesis that influence the specification of other cells in the embryo. These states, however, may not be reflected in the developmental potentials of the cells themselves. They can only be scored indirectly by their action on the specification of other cells in the embryo. Blastomeres that behave cell-autonomously in isolation are nevertheless subjected to cell-cell interactions in the embryonic context. Why this should be is an intriguing question. The classical notion has been that blastomeres are specified autonomously in nematodes. In recent years, it was established that at least five inductions are required to determine the AB descendants of C. elegans, whereas the P1 descendants have been typically viewed to develop more autonomously. It appears now that inductions also play a major role during the determination of P1-derived blastomeres.

Animals↗
PubMed1990

The effect of clenbuterol administration in utero and throughout lactation on pre- and post-natal muscle development in the rat.

The beta-adrenergic agonist, clenbuterol was fed to pregnant rats during gestation and throughout lactation. Changes in muscle morphology and composition were studied in foetal and weanling rats. Drug treatment did not affect mean foetal number, but mean foetal body weight was significantly reduced. Heart weights were increased and both muscle weight and secondary to primary fibre ratios were decreased in foetuses exposed to clenbuterol in utero. In animals exposed to clenbuterol throughout gestation and lactation, muscle weights, and protein, RNA and DNA content and total fibre numbers were reduced. In addition a drug induced anabolism was observed in the muscles of the dams. The data are discussed in terms of a direct drug effect on immature and differentiated muscle together with a possible indirect action through the repartitioning action of clenbuterol.

Adenosine Triphosphatases↗
PubMed1983

Myosin light-chain expression during avian muscle development.

Monoclonal antibodies to adult chicken myosin light chains were generated and used to quantitate the types of myosin light-chain (MLC) isoforms expressed during development of the pectoralis major (PM), anterior latissimus dorsi (ALD), and medial adductor (MA) muscles of the chicken. These are muscles which, in the adult, are composed predominantly of fast, slow, and a mixture of fiber types, respectively. Three distinct phases of MLC expression characterized the development of the PM and MA muscles. The first identifiable pase occurred during the period of 5-7 d of incubation in ovo. Extracts of muscles from the pectoral region (which included the presumptive PM muscle) contained only fast MLC isoforms. This period of exclusive fast light-chain synthesis was followed by a phase (8- 12 d of incubation in ovo) in which coexpression of both fast and slow MLC isoforms was apparent in both PM and MA muscles. During the period, the composition of both fast and slow MLC isoforms in the PM and MA muscles was identical. Beginning at day 12 in ovo, the ALD was also subjected to immunochemical analyses. The proportion of fast and slow MLCs in this muscle at day 12 was similar to that present in the other muscles studied. The third development phase of MLC expression began at approximately 12 d of incubation in ovo and encompassed the transition in MLC composition to the isoform patterns incubation in ovo and encompassed the transition in MLC composition to the isoform patterns typical of adult muscle. During this period, the relative proportion of slow MLC rose in both the MA and ALD and fell in the PM. By day 16, the third fast light chain, LC(3f), was apparent in extracts of both the PM and MA. These results show that there is a developmental progression in the expression of MLC in the two avian muscles studied from day 5 in ovo; first, only fast MLCs are accumulated, then both fast and slow MLC isoforms are expressed. Only during the latter third of development in ovo is the final MLC isoform pattern characteristic of a particular muscle type expressed.

Animals↗
PubMed2002

Influence of puberty on muscle development at the forearm.

Despite its fundamental importance for physical development, the growth of the muscle system has received relatively little consideration. In this study, we analyzed the relationship between cross-sectional area (CSA) of forearm muscles and maximal isometric grip force with age and pubertal stage. The study population comprised 366 children, adolescents, and young adults from 6 to 23 yr of age (185 female) and 107 adults (88 female) aged 29 to 40 yr. By use of peripheral quantitative computed tomography, muscle CSA was determined at the site of the forearm, whose distance to the ulnar styloid process corresponded to 65% of forearm length. Both muscle CSA and grip force were higher in prepubertal boys than in girls. The gender differences decreased until pubertal stage 3 and reincreased thereafter. In girls at pubertal stage 5, muscle CSA no longer increased with age (P > 0.4), whereas there was still some age-related increase in grip force (P = 0.02). In boys at pubertal stage 5, both muscle CSA and grip force continued to increase significantly with age (P < 0.005 each). Specific grip force (grip force per muscle CSA) adjusted for forearm length increased by almost one-half between 6 and 20 yr of age, with no difference between the genders. In conclusion, forearm muscle growth takes a gender-specific course during puberty, indicating that it is influenced by hormonal changes. However, the increase in specific grip force is similar in both genders and thus appears to be independent of sex hormones.

Adolescent↗
PubMed1981

The establishment and the subsequent elimination of polyneuronal innervation of developing muscle: theoretical considerations.

An analysis is given of the polyneuronal innervation of embryonic skeletal muscle and its subsequent elimination during development. The amount of polyneuronal innervation that has been observed is consistent with the notion that initially each motor neuron distributes its contacts at random among the available fibres of a particular muscle. The idea that the elimination of excess innervation proceeds through interactions between terminals is placed on quantitative basis. Each motor neuron is presumed to have a finite capacity for maintaining the structure and activity of its terminals, which is shared out among them; a survival strength can be assigned to each terminal. Survival strengths undergo a process of continual adjustment. A terminal with above average strength for its endplate is strengthened at the expense of the weaker terminals, subject to the total survival strength available to each motor neuron remaining constant. It is proved that this scheme will transform the initial pattern of innervation into one in which each muscle fibre has contact from a single axon. Interpretations of the following results are given: the decrease in the spread of motor unit size during the development of innervation of the rat soleus muscle; the time course of superinnervation; the effects of neonatal partial denervation. Various suggestions are made for future experimental approaches.

Animals↗
PubMed1981

Growth and muscle development of feedlot cattle of different genetic backgrounds.

The effects of crossbreeding, cattle type and dietary energy level on semitendinosus muscle (ST) development, feedlot performance, daily carcass protein and fat gain and serum anabolic hormone concentrations were studied. Over 3 consecutive years, 176 feedlot steers representing four cattle types - unselected Hereford (UH), selected Hereford (SH), Angus x Hereford x Charolais (AHC) and Angus x Hereford x Holstein (AHH) - were fed either an all-corn silage (HS) or a high grain (HG) diet. Steers were slaughtered on day 1 and at the end of the feedlot trial, and ST muscles were removed rapidly. During years 2 and 3, single blood samples were obtained from steers on days 1, 29, 57, 113 and 169, and analyzed for insulin and growth hormone (GH). Steers fed HG had a higher (P less than .005) average daily gain (ADG) than steers fed HS, and cattle type had an effect (P less than .005) on ADG. Cattle type and HG affected (P less than .005) daily carcass protein and fat gain. Weight of ST muscle and total muscle RNA, DNA and protein content increased with frame size, and HS steers had heavier (P less than .05) ST muscles than the HG steers. Steers fed HG had higher (P less than .01) serum insulin concentrations than steers fed HS, but there were no consistent cattle type effects. Serum GH concentrations were not affected by cattle type or diet. Serum insulin concentrations, combined across diet and cattle types, were correlated (P less than .01) with ADG; however, serum GH, assessed on the same basis, was not related to ADG. Average daily protein and fat gain were positively related to serum insulin and were negatively related to serum GH.

Animals↗
PubMed1980

Mutants altering coordinate synthesis of specific myosins during nematode muscle development.

Mutations in the unc-52 gene on linkage group II retard the construction of body-wall muscle sarcomeres during larval development in the nematode Caenorhabditis elegans. Unc-52 mutants show decreased accumulation of myosin heavy chains relative to other polypeptides during larval development, correlating with the structural retardation. Pulse radiolabeling experiments show that decreased synthesis of specific body-wall myosin heavy chains that are encoded by the unc-54 gene on linkage group I is responsible for the defective myosin accumulation. In the wild type, a constant ratio of the synthesis of the unc-54-coded myosin B to myosin A, about 2:1, is maintained during the larval stages in which the synthesis of both myosins increases exponentially and rapid sarcomere growth and addition ensues. During the first 26 hr of larval development, before any structural or behavioral effects of unc-52 mutations are apparent, the synthesis of myosin heavy chains is also normal. By 38 hr, decreased synthesis of myosin B is detected in the unc-52 mutant SU200, when sarcomere growth slows considerably. The effects of mutation in the unc-52 locus are trans acting upon the synthesis of unc-54-coded myosin in a specific set of muscle cells during a defined period of larval development.

Animals↗
PubMed1998

Altered smooth muscle development and innervation in the lower genitourinary and gastrointestinal tract of the male human fetus with myelomeningocele.

PURPOSE: We determine whether smooth and skeletal muscle or nerve density is altered in the lower genitourinary or gastrointestinal tract of male human fetuses with myelomeningocele at 20 weeks of gestation. MATERIALS AND METHODS: We serially cross sectioned the lower genitourinary and gastrointestinal tracts in 7 male fetuses (mean age 20 weeks of gestation) with myelomeningocele and 4 age matched controls. Immunohistochemical staining was performed using Masson's trichrome stain and antibodies to smooth and skeletal muscle actin. S-100 protein staining for Schwann cell localization and neurofilament protein was also done. Fluorescein and rhodamine double immunolabeling was used to demonstrate the co-expression of smooth and skeletal muscle. RESULTS: Peripheral neural innervation of the bladder, prostate and rectum was markedly decreased in myelomeningocele. Masson's trichrome and smooth muscle actin staining also demonstrated that smooth muscle was less well differentiated in myelomeningocele specimens. Scant smooth muscle was present in the myelomeningocele bladder and bladder neck with an excess of collagen in an interfascicular and intrafascicular distribution. Double immunofluorescence staining revealed persistent co-expression of smooth and skeletal muscle actin by myocytes in the myelomeningocele detrusor, while in the control bladder there was only smooth muscle expression. The skeletal muscle component of structures in fetuses with myelomeningocele, including the external sphincter, was similar to that in controls. Prostatic size, ductal morphogenesis and smooth muscle were decreased compared to those in controls. CONCLUSIONS: A global defect exists in the development of smooth muscle in myelomeningocele in the lower genitourinary and gastrointestinal tracts by 20 weeks of gestation. Peripheral nerve density is decreased in smooth muscle in myelomeningocele, suggesting that an intact nervous system is important for the development of normal smooth muscle. Fetal surgery with coverage of the spinal cord in select cases may prevent progressive environmental injury to the somatic nervous system during the second half of gestation. However, achieving normal autonomic function is unlikely due to the extent of early global organ maldevelopment.

Digestive System↗
PubMed1990

Change in synthesis of sulfated glycoconjugates during muscle development, maturation and aging in embryonic to senescent CBF-1 mouse.

Previous biochemical and morphological studies have demonstrated a change in the synthetic pattern of sulfated proteoglycans during skeletal musculogenesis in the embryonic chick. These studies revealed that a transition occurs in both composition and deposition of sulfated glycoconjugates that parallels the developmental state of the tissue. The current study was undertaken to ascertain whether this transition in the embryonic chick is a conserved developmental process during musculogenesis in the mouse. Leg musculature from embryonic, newborn, juvenile, adolescent, young adult, mature adult and senescent mice, radiolabeled in vivo with [35S]sulfate, was analyzed for relative size and composition of newly synthesized sulfated macromolecules. The data reveal a transition in the synthesis of sulfated proteoglycans and glycoproteins that parallels the myogenic differentiative state of the mouse leg muscle. Embryonic mouse leg musculature synthesizes relatively large proteoglycans consisting of large chondroitin sulfate glycosaminoglycan chains. Subsequently, these major newly synthesized proteoglycans are replaced synthetically by smaller molecules composed of mixtures of dermatan sulfate, chondroitin sulfate and heparan sulfate glycosaminoglycans (newborn through 2 weeks); dermatan sulfate, heparan sulfate and chondroitin sulfate glycosaminoglycans (13 months) and heparan sulfate and dermatan sulfate glycosaminoglycans (25-26 months). The sulfated glycoproteins demonstrate a reciprocal synthetic pattern. Early in development sulfated glycoproteins form a small proportion of the newly synthesized sulfated material. With increasing developmental and maturational age, the proportion of sulfated glycoproteins increases. This continues until they become the predominant sulfated moieties synthesized by senescent mouse muscle. The results from this study thus extend observations initially made in chick to muscle development in the mouse and, therefore, suggest that the transition in synthesis of sulfated glycoconjugates is a conserved developmental process during musculogenesis.

Aging↗
PubMed1990

Precocious appearance of cardiac troponin T pre-mRNAs during early avian embryonic skeletal muscle development in ovo.

Cardiac troponin T (cTNT), a component of the muscle contractile apparatus, is transiently expressed in skeletal muscle during avian limb development. While cTNT was first detected immunohistochemically in limb buds undergoing overt myogenic differentiation (Hamburger and Hamilton stage 26, about 5 days in ovo), RNA blot analyses of early, predifferentiated wing buds have revealed the presence of cTNT transcripts in limb buds as early as stage 23 (4 days in ovo). Steady-state cTNT poly(A) RNAs of stage 22 through stage 37 fore- and hindlimbs were compared using both cTNT cDNA and cTNT intron-specific probes. In the predifferentiated state, two incompletely processed RNAs (3.8 and 2.4 kb) were expressed in the absence of the mature cTNT transcript, while a third pre-mRNA (3.5 kb) appeared concomitantly with the mature mRNA as differentiation and development proceeded. In addition, a population of unique cTNT transcripts were expressed in a proximal to distal manner in wing buds which had undergone initial overt myogenic differentiation (stage 26). Some of the cTNT pre-mRNAs observed in premyogenic limbs appeared to accumulate stably in a tissue-specific manner, based on their absence from the cardiac poly(A) RNA population. These results suggest that the appearance of cardiac troponin T mRNA, as well as the polypeptide, may be regulated at multiple levels including RNA processing, stability, and/or translation during early skeletal muscle myogenesis.

Animals↗
PubMed1998

A divergent multi-domain cyclophilin is highly conserved between parasitic and free-living nematode species and is important in larval muscle development.

A divergent multi-domain cyclophilin from the filarial nematodes Brugia malayi, Onchocerca volvulus and Dirofilaria immitis has a highly conserved orthologue in the free-living nematodes Caenorhabditis elegans and C. briggsae. Cyclophilins are the receptors for the immunosuppressive and anti-parasitic agent cyclosporin A and additionally these ubiquitously expressed proteins have protein folding capabilities, and exhibit proline isomerase activity. These divergent nematode cyclophilins (CYP-4 isoforms) are three domain proteins, which share 63-88% identity and have highly conserved differences present in their functionally important cyclosporin A binding and proline isomerase domains. This unusual class of nematode cyclophilins has been studied in the model nematode C. elegans, revealing a unique temporal and spatial expression pattern. The cyp-4 transcript is most abundantly expressed in the early larval stages and is expressed exclusively in the body-wall striated muscle cells. An important functional role was established for this divergent enzyme, as specific double-stranded RNA interference experiments resulted in progeny with a phenotypically lumpy appearance. This morphological defect was predominantly expressed in the early larval stages and is consistent with an effect on body-wall muscle cell development. This study has established that this highly conserved family of nematode cyclophilins has a tissue-specific, functional role in early larval development and supports the use of C. elegans as a model for the study of orthologues in the experimentally less amenable parasitic nematodes.

Amino Acid Sequence↗
PubMed1987

Myomesin and M protein: differential expression in embryonic fibers during pectoral muscle development.

By applying immunocytochemistry using monoclonal antibodies, we found that the myofibrillar M band of both presumptive type-I and -II fibers in the pectoralis major muscle of chickens contains two high-molecular-weight proteins, i.e., myomesin (Mr, 185,000) and M protein (Mr, 165,000), early in embryonic development (7 days in ovo), even though adult type-I fibers lack M protein. The developmental expression of M protein is unusual in that, from 10 to 14 days in ovo, it is gradually suppressed not only in presumptive type-I fibers but also in presumptive type-II fibers formed from primary-generation myotubes. This latter suppression is transient, as M protein is expressed in all adult type-II fibers derived from both the primary- and second-generation myotubes. Myomesin, on the other hand, is continuously expressed in all myotubes throughout development. This finding shows that myomesin and M protein expression is regulated independently in different myotube populations, and that the suppression of M protein in primary-generation myotubes accounts for the delayed accumulation of M protein during development, as previously revealed by biochemical analysis. Presumptive type-I fibers, which form in the deep portion of the muscle, become concentrated in a narrow band known as the red strip.

Aging↗
PubMed1993

Muscle development is independent of innervation during Drosophila embryogenesis.

We have examined the role of innervation in directing embryonic myogenesis, using a mutant (prospero), which delays the pioneering of peripheral motor nerves of the Drosophila embryo. In the absence of motor nerves, myoblasts fuse normally to form syncytial myotubes, myotubes form normal attachments to the epidermis, and a larval musculature comparable to the wild-type pattern is generated and maintained. Likewise, the twist-expressing myoblasts that prefigure the adult musculature segregate normally in the absence of motor nerves, migrate to their final embryonic positions and continue to express twist until the end of embryonic development. In the absence of motor nerves, myotubes uncouple at the correct developmental stage to form single cells. Subsequently, uninnervated myotubes develop the mature electrical and contractile properties of larval muscles with a time course indistinguishable from normally innervated myotubes. We conclude that innervation plays no role in the patterning, morphogenesis, maintenance or physiological development of the somatic muscles in the Drosophila embryo.

Animals↗
PubMed1993

Cellular and molecular diversity in skeletal muscle development: news from in vitro and in vivo.

Skeletal muscle formation is studied in vitro with myogenic cell lines and primary muscle cell cultures, and in vivo with embryos of several species. We review several of the notable advances obtained from studies of cultured cells, including the recognition of myoblast diversity, isolation of the MyoD family of muscle regulatory factors, and identification of promoter elements required for muscle-specific gene expression. These studies have led to the ideas that myoblast diversity underlies the formation of the multiple types of fast and slow muscle fibers, and that myogenesis is controlled by a combination of ubiquitous and muscle-specific transcriptional regulators that may be different for each gene. We further review some unexpected results that have been obtained when ideas from work in culture have been tested in developing animals. The studies in vivo point to additional molecular and cellular mechanisms that regulate muscle formation in the animal.

Animals↗