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Muscle Development (muscle + development)
Kinds of Muscle Development Selected AbstractsBone and Muscle Development During Puberty in Girls: A Seven-Year Longitudinal Study,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2009Leiting Xu Abstract The growth of lean mass precedes that of bone mass, suggesting that muscle plays an important role in the growth of bone. However, to date, no study has directly followed the growth of bone and muscle size through puberty and into adulthood. This study aimed to test the hypothesis that the growth of muscle size precedes that of bone size (width and length) and mass during puberty. Bone and muscle properties were measured using pQCT and DXA in 258 healthy girls at baseline (mean age, 11.2 yr) and 1-, 2-, 3,4- and 7-yr follow-up. Growth trends as a function of time relative to menarche were determined from prepuberty to early adulthood for tibial length (TL), total cross-sectional area (tCSA), cortical CSA (cCSA), total BMC (tBMC), cortical volumetric BMD (cBMD), and muscle CSA (mCSA) in hierarchical models. The timings of the peak growth velocities for these variables were calculated. Seventy premenopausal adults, comprising a subset of the girl's mothers (mean age, 41.5 yr), were included for comparative purposes. In contrast to our hypothesis, the growth velocity of mCSA peaked 1 yr later than that of tibial outer dimensions (TL and tCSA) and slightly earlier than tBMC. Whereas TL ceased to increase 2 yr after menarche, tCSA, cCSA, tBMC, and mCSA continued to increase and were still significantly lower than adult values at the age of 18 yr (all p < 0.01). The results do not support the view that muscle force drives the growth of bone size during puberty. [source] The role of cell death in sexually dimorphic muscle development: Male-specific muscles are retained in female bax/bak knockout miceDEVELOPMENTAL NEUROBIOLOGY, Issue 11 2008Dena A. Jacob Abstract The bulbocavernosus (BC) and levator ani (LA) muscles are present in males but absent or severely reduced in females, and the fate of these muscles controls the survival of motoneurons in the sexually dimorphic spinal nucleus of the bulbocavernosus. However, the mechanism underlying the sex difference in BC and LA development has been controversial. We examined the role of cell death in sexual differentiation of the bulbocavernosus BC/LA muscles in mice. Muscle development was mapped from embryonic day 16 (E16) to postnatal day 5 (P5). A sex difference (male > female) first arose on E17 (BC) or E18 (LA), and increased in magnitude postnatally. TUNEL labeling revealed dying cells in the BC and LA muscles of both sexes perinatally. However, females had a significantly higher density of TUNEL-positive cells than did males. A role for the proapoptotic factors, Bax and Bak, in BC/LA development was tested by examining mice lacking one or both of these proteins. In females lacking either Bax or Bak, the BC was absent and the LA rudimentary. Deletion of both bax and bak genes, however, rescued the BC, increased LA size ,20-fold relative to controls, and virtually eliminated TUNEL-positive cells in both muscles. We conclude that cell death plays an essential role in sexual differentiation of the BC/LA muscles. The presence of either Bax or Bak is sufficient for cell death in the BC/LA, whereas the absence of both prevents sexually dimorphic muscle cell death. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source] Expression and alternative splicing of N-RAP during mouse skeletal muscle development,CYTOSKELETON, Issue 12 2008Shajia Lu Abstract N-RAP alternative splicing and protein localization were studied in developing skeletal muscle tissue from pre- and postnatal mice and in fusing primary myotubes in culture. Messages encoding N-RAP-s and N-RAP-c, the predominant isoforms of N-RAP detected in adult skeletal muscle and heart, respectively, were present in a 5:1 ratio in skeletal muscle isolated from E16.5 embryos. N-RAP-s mRNA levels increased three-fold over the first 3 weeks of postnatal development, while N-RAP-c mRNA levels remained low. N-RAP alternative splicing during myotube differentiation in culture was similar to the pattern observed in embryonic and neonatal muscle, with N-RAP-s expression increasing and N-RAP-c mRNA levels remaining low. In both developing skeletal muscle and cultured myotubes, N-RAP protein was primarily associated with developing myofibrillar structures containing ,-actinin, but was not present in mature myofibrils. The results establish that N-RAP-s is the predominant spliced form of N-RAP present throughout skeletal muscle development. Cell Motil. Cytoskeleton 2008. Published 2008 Wiley-Liss, Inc. [source] Cell adhesion in zebrafish myogenesis: Distribution of intermediate filaments, microfilaments, intracellular adhesion structures and extracellular matrixCYTOSKELETON, Issue 10 2008Manoel L. Costa Abstract To overcome the limitations of in vitro studies, we have been studying myogenesis in situ in zebrafish embryos, at a sub-cellular level. While in previous works we focused on myofibrillogenesis and some aspects of adhesion structures, here we describe in more detail cell adhesion structures and interactions among cytoskeletal components, membrane and extracellular matrix during zebrafish muscle development. We studied the intermediate filaments, and we describe the full range of desmin distribution in zebrafish development, from perinuclear to striated, until its deposition around the intersomite septa of older somites. This adhesion structure, positive for desmin and actin, has not been previously observed in myogenesis in vitro. We also show that actin is initially located in the intersomite septum region whereas it is confined to the myofibrils later on. While actin localization changes during development, the adhesion complex proteins vinculin, paxillin, talin, dystrophin, laminin and fibronectin always appear exclusively at the intersomite septa, and appear to be co-distributed, even though the extracellular proteins accumulates before the intracellular ones. Contrary to the adhesion proteins, that are continuously distributed, desmin and sarcomeric actin form triangular aggregates among the septa and the cytoskeleton. We studied the cytoskeletal linker plectin as well, and we show that it has a distribution similar to desmin and not to actin. We conclude that the in situ adhesion structures differ from their in vitro counterparts, and that the actual zebrafish embryo myogenesis is quite different than that which occurs in in vitro systems. Cell Motil. Cytoskeleton 65: 801,815, 2008. © 2008 Wiley-Liss, Inc. [source] Nesprins, but not sun proteins, switch isoforms at the nuclear envelope during muscle developmentDEVELOPMENTAL DYNAMICS, Issue 3 2010K. Natalie Randles Abstract Nesprins are a family of nuclear transmembrane proteins anchored via Sun proteins to the nuclear membrane. Analysis of nesprins during human muscle development revealed an increase in nesprin-1-giant during early myogenesis in vitro. During the transition from immature to mature muscle fibres in vivo, nesprin-2 partly replaced nesprin-1 at the nuclear envelope and short nesprin isoforms became dominant. Sun1 and Sun2 proteins remained unchanged during this fibre maturation. In emerin-negative skin fibroblasts, nesprin-2-giant was relocated from the nuclear envelope to the cytoplasm, not to the endoplasmic reticulum, while nesprin-1 remained at the nuclear envelope. In emerin-negative keratinocytes lacking nesprin-1, nesprin-2 remained at the nuclear envelope. HeLa cell nuclear envelopes lacked nesprin-1, which was the dominant form in myoblasts, while a novel 130-kD nesprin-2 isoform dominated Ntera-2 cells. The results suggest the possibility of isoform-specific and tissue-specific roles for nesprins in nuclear positioning. Developmental Dynamics 239:998,1009, 2010. © 2010 Wiley-Liss, Inc. [source] Molecular mechanisms of mechanosensing in muscle developmentDEVELOPMENTAL DYNAMICS, Issue 6 2009Klodiana Jani Abstract Mechanical forces are crucial to muscle development and function, but the mechanisms by which forces are sensed and transduced remain elusive. Evidence implicates the sarcolemmal lattice of integrin adhesion and the Z-disk components of the contractile machinery in such processes. These mechanosensory devices report changes in force to other cellular compartments by self-remodeling. Here we explore how their structural and functional properties integrate to regulate muscle development and maintenance. Developmental Dynamics 238:1526,1534, 2009. © 2009 Wiley-Liss, Inc. [source] Analysis of human muscle stem cells reveals a differentiation-resistant progenitor cell population expressing Pax7 capable of self-renewalDEVELOPMENTAL DYNAMICS, Issue 1 2009Bradley Pawlikowski Abstract Studies using mouse models have established a critical role for resident satellite stem cells in skeletal muscle development and regeneration, but little is known about this paradigm in human muscle. Here, using human muscle stem cells, we address their lineage progression, differentiation, migration, and self-renewal. Isolated human satellite cells expressed ,7-integrin and other definitive muscle markers, were highly motile on laminin substrates and could undergo efficient myotube differentiation and myofibrillogenesis. However, only a subpopulation of the myoblasts expressed Pax7 and displayed a variable lineage progression as measured by desmin and MyoD expression. Analysis identified a differentiation-resistant progenitor cell population that was Pax7+/desmin, and capable of self-renewal. This study extends our understanding of the role of Pax7 in regulating human satellite stem cell differentiation and self-renewal. Developmental Dynamics 238:138,149, 2009. © 2008 Wiley-Liss, Inc. [source] From segment to somite: Segmentation to epithelialization analyzed within quantitative frameworksDEVELOPMENTAL DYNAMICS, Issue 6 2007Paul M. Kulesa Abstract One of the most visually striking patterns in the early developing embryo is somite segmentation. Somites form as repeated, periodic structures in pairs along nearly the entire caudal vertebrate axis. The morphological process involves short- and long-range signals that drive cell rearrangements and cell shaping to create discrete, epithelialized segments. Key to developing novel strategies to prevent somite birth defects that involve axial bone and skeletal muscle development is understanding how the molecular choreography is coordinated across multiple spatial scales and in a repeating temporal manner. Mathematical models have emerged as useful tools to integrate spatiotemporal data and simulate model mechanisms to provide unique insights into somite pattern formation. In this short review, we present two quantitative frameworks that address the morphogenesis from segment to somite and discuss recent data of segmentation and epithelialization. Developmental Dynamics 236:1392,1402, 2007. © 2007 Wiley-Liss, Inc. [source] Potential roles for BMP and Pax genes in the development of iris smooth muscleDEVELOPMENTAL DYNAMICS, Issue 2 2005Abbie M. Jensen Abstract The embryonic optic cup generates four types of tissue: neural retina, pigmented epithelium, ciliary epithelium, and iris smooth muscle. Remarkably little attention has focused on the development of the iris smooth muscle since Lewis ([1903] J. Am. Anat. 2:405,416) described its origins from the anterior rim of the optic cup neuroepithelium. As an initial step toward understanding iris smooth muscle development, I first determined the spatial and temporal pattern of the development of the iris smooth muscle in the chick by using the HNK1 antibody, which labels developing iris smooth muscle. HNK1 labeling shows that iris smooth muscle development is correlated in time and space with the development of the ciliary epithelial folds. Second, because neural crest is the only other neural tissue that has been shown to generate smooth muscle (Le Lievre and Le Douarin [1975] J. Embryo. Exp. Morphol. 34:125,154), I sought to determine whether iris smooth muscle development shares similarities with neural crest development. Two members of the BMP superfamily, BMP4 and BMP7, which may regulate neural crest development, are highly expressed by cells at the site of iris smooth muscle generation. Third, because humans and mice that are heterozygous for Pax6 mutations have no irides (Hill et al. [1991] Nature 354:522,525; Hanson et al. [1994] Nat. Genet. 6:168,173), I determined the expression of Pax6. I also examined the expression of Pax3 in the developing anterior optic cup. The developing iris smooth muscle coexpresses Pax6 and Pax3. I suggest that some of the eye defects caused by mutations in Pax6, BMP4, and BMP7 may be due to abnormal iris smooth muscle. Developmental Dynamics 232:385,392, 2005. © 2004 Wiley-Liss, Inc. [source] Novel metalloprotease,disintegrin, meltrin , (ADAM35), expressed in epithelial tissues during chick embryogenesisDEVELOPMENTAL DYNAMICS, Issue 3 2004Mitsuko Watabe-Uchida Abstract Members of the ADAM (adisintegrin and metalloprotease) family are involved in fertilization, morphogenesis, and pathogenesis. Their metalloprotease domains mediate limited proteolysis, including ectodomain shedding of membrane-anchored growth factors and intercellular-signaling proteins, and their disintegrin domains play regulatory roles in cell adhesion and migration. In screening for cDNAs encoding chicken ADAM proteins expressed during muscle development, we identified Meltrin , as a novel member of this family. To elucidate its functions, we investigated its expression during development by using antibodies raised against its protease domain. In the somites, Meltrin , protein was specifically expressed in the myotomal cells, which delaminate from the dermomyotome to form epithelial sheets. It was also found in the surface ectoderm, lens placodes, otic vesicles, and the gut epithelia. Basolateral localization of Meltrin , in these epithelial cells suggests its unique roles in the organization of the epithelial tissues and development of the sensory organs and the gut. Developmental Dynamics 230:557,568, 2004. © 2004 Wiley-Liss, Inc. [source] The role of cell death in sexually dimorphic muscle development: Male-specific muscles are retained in female bax/bak knockout miceDEVELOPMENTAL NEUROBIOLOGY, Issue 11 2008Dena A. Jacob Abstract The bulbocavernosus (BC) and levator ani (LA) muscles are present in males but absent or severely reduced in females, and the fate of these muscles controls the survival of motoneurons in the sexually dimorphic spinal nucleus of the bulbocavernosus. However, the mechanism underlying the sex difference in BC and LA development has been controversial. We examined the role of cell death in sexual differentiation of the bulbocavernosus BC/LA muscles in mice. Muscle development was mapped from embryonic day 16 (E16) to postnatal day 5 (P5). A sex difference (male > female) first arose on E17 (BC) or E18 (LA), and increased in magnitude postnatally. TUNEL labeling revealed dying cells in the BC and LA muscles of both sexes perinatally. However, females had a significantly higher density of TUNEL-positive cells than did males. A role for the proapoptotic factors, Bax and Bak, in BC/LA development was tested by examining mice lacking one or both of these proteins. In females lacking either Bax or Bak, the BC was absent and the LA rudimentary. Deletion of both bax and bak genes, however, rescued the BC, increased LA size ,20-fold relative to controls, and virtually eliminated TUNEL-positive cells in both muscles. We conclude that cell death plays an essential role in sexual differentiation of the BC/LA muscles. The presence of either Bax or Bak is sufficient for cell death in the BC/LA, whereas the absence of both prevents sexually dimorphic muscle cell death. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source] Cell fate and timing in the evolution of neural crest and mesoderm development in the head region of amphibians and lungfishesACTA ZOOLOGICA, Issue 2009Rolf Ericsson Abstract Our research on the evolution of head development focuses on understanding the developmental origins of morphological innovations and involves asking questions like: How flexible (or conserved) are cell fates, patterns of cell migration or the timing of developmental events (heterochrony)? How do timing changes, or changes in life history affect head development and growth? Our ,model system' is a comparison between lungfishes and representatives from all three extant groups of amphibians. Within anuran amphibians, major changes in life history such as the repeated evolution of larval specializations (e.g. carnivory), or indeed the loss of a free-swimming larva, allows us to test for developmental constraints. Cell migration and cell fate are conserved in cranial neural crest cells in all vertebrates studied so far. Patterning and developmental anatomy of cranial neural crest and head mesoderm cells are conserved within amphibians and even between birds, mammals and amphibians. However, the specific formation of hypobranchial muscles from ventral somitic processes shows variation within tetrapods. The evolution of carnivorous larvae in terminal taxa is correlated with changes in both pattern and timing of head skeletal and muscle development. Sequence-heterochronic changes are correlated with feeding mode in terminal taxa and with phylogenetic relatedness in basal branches of the phylogeny. Eye muscles seem to form a developmental module that can evolve relatively independently from other head muscles, at least in terms of timing of muscle differentiation. [source] Protease-Activated Receptors: A Means of Converting Extracellular Proteolysis into Intracellular SignalsIUBMB LIFE, Issue 6 2002E. J. Mackie Abstract Protease-activated receptors (PARs) mediate cellular responses to a variety of extracellular proteases. The four known PARs constitute a subgroup of the family of seven-transmembrane domain G protein-coupled receptors and activate intracellular signalling pathways typical for this family of receptors. Activation of PARs involves proteolytic cleavage of the extracellular domain, resulting in formation of a new N terminus, which acts as a tethered ligand. PAR-1, -3, and -4 are relatively selective for activation by thrombin whereas PAR-2 is activated by a variety of proteases, including trypsin and tryptase. Recent studies in mice genetically incapable of expressing specific PARs have defined roles for PAR-1 in vascular development, and for PAR-3 and -4 in platelet activation, which plays a fundamental role in blood coagulation. PAR-1 has also been implicated in a variety of other biological processes including inflammation, and brain and muscle development. Responses mediated by PAR-2 include contraction of intestinal smooth muscle, epithelium-dependent smooth muscle relaxation in the airways and vasculature, and potentiation of inflammatory responses. The area of PAR research is rapidly expanding our understanding of how cells communicate and control biological functions, in turn increasing our knowledge of disease processes and providing potential targets for therapeutic intervention. [source] Simultaneous genotyping to detect myostatin gene polymorphism in beef cattle breedsJOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 6 2002M. E. Miranda Summary The myostatin gene codes for a growth factor involved in muscle development, and polymorphism in this gene can have important economic consequences. Nine mutations affecting the amino-acidic sequence have already been described, six of which are disruptive, inactivating the protein and causing bovine muscular hypertrophy. As the number of known mutations grows, it is necessary to develop a simple, routinely usable technique able to screen individuals in all populations. The oligonucleotide ligation assay (OLA) is proposed here for the rapid genotyping of the nine mutations known affecting the coding sequence in the main breeds of beef cattle. This technique showed its ability to reveal the genotype of individuals being a good tool to determine the frequency of each mutation in a population. The procedure is very flexible as new mutations can be added and removed at any time. Depending on the genotype of each individual, the technique allows breeders to make quick decisions on matings and general selection tendencies. Zusammenfassung Simultane Genotypisierung von Polymorphismen im Myostatin-Gen in Fleischrinderrassen Das Myostatin-Gen kodiert für einen Wachstumsfaktor, der in die Muskelentwicklung eingebunden ist und Polymorphismen in diesem Gen können daher wichtige ökonomische Konsequenzen haben. Bisher wurden neun Mutationen, die Auswirkungen auf die Aminosäuresequenz haben, beschrieben. Sechs davon inaktivieren das Protein und verursachen bovine muskuläre Hypertrophie. Da die Anzahl der bekannten Mutationen in diesem Gen steigt, ist es notwendig, eine einfache, in der Routine einsetzbare Methode zu entwickeln, um Individuen in allen Populationen untersuchen zu können. Zur schnellen Genotypisierung der neun bekannten Mutationen, welche die kodierende Sequenz in den Hauptfleischrinderrassen betreffen, wird hier der Oligo-Ligationsassay (OLA) vorgeschlagen. Durch diese Technik ist es möglich, den Genotyp jedes Individuums und die Frequenz jeder einzelnen Mutation in der Population festzustellen. Die Prozedur ist sehr flexibel, da zu jedem Zeitpunkt neue Mutationen hinzugefügt bzw. weggelassen werden können. Diese Methode erlaubt dem Züchter, in Abhängigkeit vom Genotyp jedes Individiums schnelle Entscheidungen über die Anpaarung und die allgemeine Selektionsrichtung zu treffen. [source] Development-dependent disappearance of caspase-3 in skeletal muscle is post-transcriptionally regulatedJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2002Louis-Bruno Ruest Abstract Caspase-3, a major player in apoptosis, engages apoptosis-activated cells into an irreversible pathway leading to cell death. In this article, we report that caspase-3 protein is absent from rat and mouse adult skeletal muscles, despite the abundant presence of its mRNA. During skeletal muscle development, caspase-3 protein is present in neonatal animals, but its expression gradually decreases, and disappears completely by 1 month of age, when there is still abundant caspase-3 mRNA. This discordance between caspase-3 message and protein expression is unique to skeletal muscle, as in all other analyzed tissues the protein presence correlates with the presence of the mRNA. The only circumstance in which caspase-3 protein appears in adults is in regenerating muscles; once regeneration is complete, however, it again becomes undetectable in repaired muscles. We conclude that caspase-3 protein in skeletal muscle is uniquely regulated at the post-transcriptional level, unseen in other tissues such as brain, heart, lung, kidney, thymus, spleen, liver, or testis. The post-transcriptional regulation of caspase-3 might serve as a fail-safe mechanism to avoid accidental cell death. J. Cell. Biochem. 86: 21,28, 2002. © 2002 Wiley-Liss, Inc. [source] p75NTR -mediated signaling promotes the survival of myoblasts and influences muscle strengthJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2005Shailaja Reddypalli During muscle development, the p75NTR is expressed transiently on myoblasts. The temporal expression pattern of the receptor raises the possibility that the receptor is influencing muscle development. To test this hypothesis, p75NTR -deficient mutant mice were tested for muscle strength by using a standard wire gripe strength test and were found to have significantly decreased strength relative to that of normal mice. When normal mybolasts were examined in vivo for expression of NGF receptors, p75NTR was detected on myoblasts but the high affinity NGF receptor, trk A, was not co-expressed with p75NTR. In vitro, proliferating C2C12 and primary myoblasts co-expressed the p75NTR and MyoD, but immunofluorescent analysis of primary myoblasts and RT-PCR analysis of C2C12 mRNA revealed that myoblasts were devoid of trk A. In contrast to the cell death functions that characterize the p75NTR in neurons, p75NTR -positive primary and C2C12 myoblasts did not differentiate or undergo apoptosis in response to neurotrophins. Rather, myoblasts survived and even proliferated when grown at subconfluent densities in the presence of the neurotrophins. Furthermore, when myoblasts treated with NGF were lysed and immunoprecipitated with antibodies against phosphorylated I-,B and AKT, the cells contained increased levels of both phospho-proteins, both of which promote cell survival. By contrast, neurotrophin-treated myoblasts did not induce phosphorylation of Map Kinase p42/44 or p38, indicating the survival was not mediated by the trk A receptor. Taken together, the data indicate that the p75NTR mediates survival of myoblasts prior to differentiation and that the activity of this receptor during myogenesis is important for developing muscle. © 2005 Wiley-Liss, Inc. [source] Myogenic regulatory factors Myf5 and Mrf4 of fish: current status and perspectiveJOURNAL OF FISH BIOLOGY, Issue 8 2008Y. H. Chen Recent advances in the understanding of fish myogenic regulatory factors (MRF) are described in this review. Specifically, two of the MRFs are discussed, Myf5 and Mrf4, which are encoded by a highly linked gene loci (mrf4 and myf5) that is conserved among vertebrates. Experiments related to the expression patterns, biological functions and regulatory network of mrf4 and myf5 are highlighted, and examples of gene organizations and protein features among known vertebrate species are outlined. Furthermore, the complicated regulatory mechanisms of myf5 are discussed using zebrafish Danio rerio as a model. Multiple regulatory elements that control the specific expression of zebrafish myf5 are elucidated, including enhancer, silencer, proximal and distal elements, the interaction between proximal regulatory cassette ,82/,62 and its cognate binding transcription factors, and a plausible post-transcriptional regulatory mechanism. This review article highlights a fundamental molecular mechanism of mrf4 and myf5 during fish muscle development. [source] Patterns of spatial and temporal cranial muscle development in the African clawed frog, Xenopus laevis (Anura: Pipidae)JOURNAL OF MORPHOLOGY, Issue 9 2007Janine M. Ziermann Abstract The African Clawed Toad, Xenopus laevis, has been a major vertebrate model organism for developmental studies for half a century. Because most studies have focused on the early stages of development, this has had the effect that many aspects of organogenesis and later development remain relatively poorly known in this species. In particular, little is known about cranial muscle development even at the level of morphology and histological differentiation of muscle anlagen and muscle fibers. In this study, we document the morphogenesis and histological differentiation of cranial muscles in X. laevis. We provide a detailed account of the timing of development for each of the cranial muscles, and also describe a new muscle, the m. transversus anterior. The cranial musculature of X. laevis larvae generally develops in a rostrocaudal sequence. The first muscles to differentiate are the extrinsic eye muscles. Muscles of the mandibular and hyoid arches develop almost simultaneously, and are followed by the muscles of the branchial arches and the larynx, and by the mm. geniohyoideus and rectus cervicis. Despite the fact that differentiation starts at different stages in the different muscles, most are fully developed at Stage 14. These baseline data on the timing of muscle differentiation in the X. laevis can serve as a foundation for comparative studies of heterochronic changes in cranial muscle development in frogs and other lissamphibians. J. Morphol., 2007. © 2007 Wiley-Liss, Inc. [source] Influence of muscular activity on local mineralization patterns in metatarsals of the embryonic mouseJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2000E. Tanck This study addressed the theory that local mechanical loading may influence the development of embryonic long bones. Embryonic mouse metatarsal rudiments were cultured as whole organs, and the geometry of the primary ossification center was compared with that of rudiments that had developed in utero. The mineralization front in vivo was found to be nearly straight, whereas in vitro it acquired a more convex shape due to a slower mineralization rate at the periphery of the mineralized cylinder. A poroelastic finite element analysis was performed to calculate the local distributions of distortional strain and fluid pressure at the mineralization front in the metatarsal during loading in vivo as a result of muscle contractions in the embryonic hindlimbs. The distribution of fluid pressure from the finite element analysis could not explain the difference in mineralization shape. The most likely candidate for the difference was the distortional strain, resulting from muscle contraction, which is absent in vitro, because its value at the periphery was significantly higher than in the center of the tissue. Without external loads, the mineralization process may be considered as pre-programmed, starting at the center of the tissue and resulting in a spherical mineralization front. Strain modulates the rate of the mineralization process in vivo, resulting in the straight mineralization front. These results confirm that disturbances in muscle development are likely to produce disturbed mineralization patterns, resulting in a disordered osteogenic process. [source] Clenbuterol increases muscle fiber size and GATA-2 protein in rat skeletal muscle in uteroMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 5 2008Diane Downie Abstract Certain ,2 -adrenoceptor agonists, such as clenbuterol, are known to elicit a muscle-specific anabolism or hypertrophy in both normal and catabolic muscle in a wide variety of species. However, the underlying mechanism(s) of the ,2 -agonist-induced anabolism remains unclear. This study aimed to determine the effects of clenbuterol administration in utero on skeletal muscle and to examine the underlying molecular mechanisms. Pregnant rats were fed clenbuterol (2 mg/kg diet) from Day 4 of gestation (4 dg) until weanling and fetal samples were taken from 13.5, 15.5, 17.5, and 19.5 dg and from 1d neonatal pups. Muscles were analyzed for total DNA, RNA and protein and sections examined morphologically for changes in muscle development. Western and immunohistochemical analyses were performed to identify changes in known myogenic signaling proteins. Clenbuterol increased the size of both fast and slow fibers in utero which was associated with a decreased DNA:protein ratio (28%) and an increased RNA:DNA ratio (36%). Additionally, drug treatment in utero induced a decrease in the fast:slow fiber ratio (38%). These myogenic changes were correlated with an increase in the GATA-2 hypertrophic transcription factor at both 17.5 dg (by 250%) and 19.5 dg (by 40%) in fetuses from clenbuterol treated dams. In addition, drug treatment resulted in increased membrane association of PKC-µ at 17.5 dg (325%) and increased PKC-, cytosolic abundance (40%) and PKC-, membrane abundance at 19.5 dg (250%). These results are the first demonstration that ,2 -agonists such as clenbuterol may act through upregulating the GATA-2 transcription factor and implicate certain PKC isoforms in the drug-induced regulation of skeletal muscle development. Mol. Reprod. Dev. 75: 785,794, 2008. © 2007 Wiley-Liss, Inc. [source] Identification of serine 205 as a site of phosphorylation on Pax3 in proliferating but not differentiating primary myoblastsPROTEIN SCIENCE, Issue 11 2008Patrick J. Miller Abstract Pax3, a member of the paired class homeodomain family of transcription factors, is essential for early skeletal muscle development. Previously, others and we have shown that the stability of Pax3 is regulated on a post-translational level. Evidence in the literature and from our laboratory suggests that phosphorylation, a common form of regulation, may play a role. However, at present, the sites of Pax3 phosphorylation are not known. We demonstrate here the first evidence that Pax3 exists as a phosphoprotein in proliferating mouse primary myoblasts. Using an in vitro kinase assay, deletion, and point mutant analysis, we conclusively identify Ser205 as a site of phosphorylation. The phosphorylation of Ser205 on endogenously expressed Pax3 was confirmed in vivo using antibodies specific for phosphorylation at Ser205. Finally, we demonstrate for the first time that the phosphorylation status of endogenous Pax3 changes rapidly upon the induction of myogenic differentiation. The presence of phosphorylation in a region of Pax3 important for mediating protein,protein interactions, and the fact that phosphorylation is lost upon induction of differentiation, allow for speculation on the biological relevance of phosphorylation. [source] In vivo proteome dynamics during early bovine myogenesisPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 20 2008Thibault Chaze Abstract Myogenesis is a complex process of which the underlying mechanisms are conserved between species, including birds and mammals. Despite a good understanding of the stages of myogenesis, many of the mechanisms involved in the regulation of proliferation of the successive myoblast generations, the cellular transitions cell proliferation/alignment of myoblasts/fusion of myoblasts into myotubes/differentiation of myofibres and the control of total myofibre number still remain unknown. An in vivo proteomic analysis of the semitendinosus muscle from Charolais foetuses, at three specific stages of myogenesis (60, 110 and 180,days postconception), was conducted using 2-DE and MS. Expression profiles of more than 170 proteins were revealed and analysed using two way hierarchical clustering and statistical analysis. Our studies identify, for the first time, distinct proteins of varied biological functions and protein clusters with myogenic processes, such as the control of cell cycle activity and apoptosis, the establishment of cellular metabolism and muscle contractile properties and muscle cell reorganisation. These results are of fundamental interest to the field of myogenesis in general, and more specifically to the control of muscle development in meat producing animals. [source] AMP-activated protein kinase signalling pathways are down regulated and skeletal muscle development impaired in fetuses of obese, over-nourished sheepTHE JOURNAL OF PHYSIOLOGY, Issue 10 2008Mei J. Zhu Maternal obesity and over-nutrition give rise to both obstetric problems and neonatal morbidity. The objective of this study was to evaluate effects of maternal obesity and over-nutrition on signalling of the AMP-activated protein kinase (AMPK) pathway in fetal skeletal muscle in an obese pregnant sheep model. Non-pregnant ewes were assigned to a control group (Con, fed 100% of NRC nutrient recommendations, n= 7) or obesogenic group (OB, fed 150% of National Research Council (NRC) recommendations, n= 7) diet from 60 days before to 75 days after conception (term 150 days) when fetal semitendinosus skeletal muscle (St) was sampled. OB mothers developed severe obesity accompanied by higher maternal and fetal plasma glucose and insulin levels. In fetal St, activity of phosphoinositide-3 kinase (PI3K) associated with insulin receptor substrate-1 (IRS-1) was attenuated (P < 0.05), in agreement with the increased phophorylation of IRS-1 at serine 1011. Phosphorylation of AMP-activated protein kinase (AMPK) at Thr 172, acetyl-CoA carboxylase at Ser 79, tuberous sclerosis 2 at Thr 1462 and eukaryotic translation initiation factor 4E-binding protein 1 at Thr 37/46 were reduced in OB compared to Con fetal St. No difference in energy status (AMP/ATP ratio) was observed. The expression of protein phosphatase 2C was increased in OB compared to Con fetal St. Plasma tumour necrosis factor , (TNF,) was increased in OB fetuses indicating an increased inflammatory state. Expression of peroxisome proliferator-activated receptor , (PPAR,) was higher in OB St, indicating enhanced adipogenesis. The glutathione: glutathione disulphide ratio was also lower, showing increased oxidative stress in OB fetal St. In summary, we have demonstrated decreased signalling of the AMPK system in skeletal muscle of fetuses of OB mothers, which may play a role in altered muscle development and development of insulin resistance in the offspring. [source] MicroRNA identity and abundance in porcine skeletal muscles determined by deep sequencingANIMAL GENETICS, Issue 2 2010M. Nielsen Summary MicroRNAs (miRNA) are short single-stranded RNA molecules that regulate gene expression post-transcriptionally by binding to complementary sequences in the 3, untranslated region (3, UTR) of target mRNAs. MiRNAs participate in the regulation of myogenesis, and identification of the complete set of miRNAs expressed in muscles is likely to significantly increase our understanding of muscle growth and development. To determine the identity and abundance of miRNA in porcine skeletal muscle, we applied a deep sequencing approach. This allowed us to identify the sequences and relative expression levels of 212 annotated miRNA genes, thereby providing a thorough account of the miRNA transcriptome in porcine muscle tissue. The expression levels displayed a very large range, as reflected by the number of sequence reads, which varied from single counts for rare miRNAs to several million reads for the most abundant miRNAs. Moreover, we identified numerous examples of mature miRNAs that were derived from opposite sides of the same predicted precursor stem-loop structures, and also observed length and sequence heterogeneity at the 5, and 3, ends. Furthermore, KEGG pathway analysis suggested that highly expressed miRNAs are involved in skeletal muscle development and regeneration, signal transduction, cell-cell and cell-extracellular matrix communication and neural development and function. [source] Identification and characterization of microRNAs from porcine skeletal muscleANIMAL GENETICS, Issue 2 2010S. S. Xie Summary MicroRNAs (miRNAs) are a class of non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. There is increasing evidence to suggest that miRNAs participate in muscle development in mice and humans; however, few studies have focused on miRNAs in porcine muscle tissue. Here, we experimentally detected and identified conserved and unique miRNAs from porcine skeletal muscle. Fifty-seven distinct miRNAs were identified, of which 39 have not been reported earlier in the pig. Of these, two miRNAs appear to be novel and pig-specific. Surprisingly, these two differ only by a single nucleotide. A part of their primary transcript was cloned and confirmed by sequencing analysis. Alignment of the two sequences using ClustalW showed that the precursor sequences were almost identical, but the flanking sequences were different, indicating that these two novel miRNAs may represent rapidly evolving miRNAs in the pig genome. The expression patterns of eight miRNAs were characterized by real-time polymerase chain reaction of eight pig tissue samples. The ssc-let-7e and ssc-miR-181b miRNAs were expressed in all tissues analysed. The ssc-let-7c, ssc-miR-125b, ssc-miR-new1 and ssc-miR-new2 miRNAs were expressed in several tissues, while ssc-miR-122 and ssc-miR-206 were specifically expressed in the liver and muscle respectively. Our results add to existing data on porcine miRNAs and are useful for investigating the biological functions of miRNAs in porcine skeletal muscle development. [source] Characterization of the porcine AMPK alpha 2 catalytic subunitgene (PRKAA2): genomic structure, polymorphism detection and association studyANIMAL GENETICS, Issue 2 2010L. Lin Summary AMP-activated protein kinase (AMPK), known as a key regulator of cellular energy homeostasis, plays an important role in regulation of glucose and lipid metabolism, and protein synthesis in mammals. The characterization of porcine PRKAA2 encoding the alpha 2 catalytic subunit of AMPK is reported in this study. PRKAA2 was assigned to porcine chromosome 6q by analysis of radiation hybrids (IMpRH panel), and its genomic structure was determined by BAC sequencing. PRKAA2 spans more than 62 kb and consists of nine exons and eight introns. A total of 25 polymorphisms were identified by re-sequencing approximately 7 kb, including all the exons, exon,intron boundaries and 5, and 3, gene flanking regions using twelve founder animals of a Mangalitsa × Piétrain intercross. Neither of two single nucleotide polymorphisms (SNPs) found in the coding region caused an amino acid substitution. Two SNPs (NM_214266.1: c.236+142A>G and NM_214266.1: c.630C>T) in PRKAA2 were genotyped in the Mangalitsa × Piétrain F2 cross (n = 589) and two commercial populations [Piétrain (n = 1173) and German Landrace (n = 536)] and evaluated for association with traits of interest (muscle development and fat deposition). Single SNP and haplotype analyses revealed weak associations between the PRKAA2 genotypes and loin muscle area in the investigated populations. [source] Discovery, characterization and validation of single nucleotide polymorphisms within 206 bovine genes that may be considered as candidate genes for beef production and qualityANIMAL GENETICS, Issue 4 2009J. L. Williams Summary A large number of putative single nucleotide polymorphisms (SNPs) have been identified from the bovine genome-sequencing project. However, few of these have been validated and many will turn out to be sequencing artefacts or have low minor allele frequencies. In addition, there is little information available on SNPs within coding regions, which are likely to be responsible for phenotypic variation. Therefore, additional SNP discovery is necessary to identify and validate polymorphisms both in specific genes and genome-wide. Sequence-tagged sites within 286 genes were resequenced from a panel of animals representing a wide range of European cattle breeds. For 80 genes, no polymorphisms were identified, and 672 putative SNPs were identified within 206 genes. Fifteen European cattle breeds (436 individuals plus available parents) were genotyped with these putative SNPs, and 389 SNPs were confirmed to have minor allele frequencies above 10%. The genes containing SNPs were localized on chromosomes by radiation hybrid mapping and on the bovine genome sequence by Blast. Flanking microsatellite loci were identified, to facilitate the alignment of the genes containing the SNPs in relation to mapped quantitative trait loci. Of the 672 putative SNPs discovered in this work, only 11 were found among the validated SNPs and 100 were found among the approximately 2.3 million putative SNPs currently in dbSNP. The genes studied in this work could be considered as candidates for traits associated with beef production and the SNPs reported will help to assess the role of the genes in the genetic control of muscle development and meat quality. The allele frequency data presented allows the general utility of the SNPs to be assessed. [source] Mapping and expression analyses during porcine foetal muscle development of 12 genes involved in histone modificationsANIMAL GENETICS, Issue 2 2009Y. B. Peng Summary Histone modifications (methylation and demethylation) regulate gene expression and play a role in cell proliferation and differentiation by their actions on chromatin structure. In this context, we studied the temporal expression profiles of genes acting on histone methylation and demethylation during skeletal muscle proliferation and differentiation. Quantitative real-time PCR was used to quantify the mRNA levels of CARM1, JARID1A, JMJD2A, LSD1, PRMT2, PRMT5, SMYD1, SMYD2, SMYD3, SETDB1, Suv39h2 and SUZ12 in foetal skeletal muscle. Our results showed that CARM1, JARID1A, JMJD2A, SMYD1 and SMYD2 were differentially expressed in embryonic muscles of 33 days post-conception (dpc), 65 dpc and 90 dpc. These 12 genes were mapped to porcine chromosomes (SSC) 2q21,24, 5q25, 6q35, 6q12,21, 6p15, 7q21, 3q21,27, 9q26, 10p16, 4q15,16, 10q14,16 and 12p12 respectively. Taking into account the reported QTL mapping results, gene expression analysis and radiation hybrid mapping results, these results suggest that five genes (CARM1, JARID1A, JMJD2A, SMYD1 and SMYD2) could be good candidate genes for growth and backfat thickness traits. [source] Genetic variation in the bovine myostatin gene in UK beef cattle: Allele frequencies and haplotype analysis in the South DevonANIMAL GENETICS, Issue 5 2000J A Smith Work on Belgian Blue cattle revealed that an 11 base pair (bp) deletion within the bovine myostatin gene (GDF8) is associated with the double-muscled phenotype seen in this breed. Investigations focusing on other European breeds known to show double-muscling identified several mutations within the coding region of the gene associated with the double-muscled phenotype in different breeds. The number of mutations found suggest that myostatin is highly variable within beef cattle. Variations that alter the structure of the gene product such that the protein is inactivated are associated with the most pronounced form of double-muscling as seen in the Belgian Blue. However, other mutations may have a less extreme affect on muscle development. While overt double-muscling gives rise to a high incidence of dystocia (calving difficulty), it is possible that some variants may give enhanced muscling, but with limited calving problems. We describe sequence analysis of the myostatin gene in ten beef breeds commonly used in the UK and show that the 11-bp deletion responsible for double-muscling in the Belgian Blue is also present in the South Devon cattle population. Allele frequencies and haplotypes in the South Devon and a polymerase chain reaction (PCR) based test for the deletion are described. PCR amplification across the deleted region provides a quick and effective test with clear identification of heterozygous individuals. We discuss our results with regard to the effect of genotype on phenotype and differences observed between the Belgian Blue and the South Devon. [source] Myostatin down-regulates the IGF-2 expression via ALK-Smad signaling during myogenesis in cattleANIMAL SCIENCE JOURNAL, Issue 2 2010Masato MIYAKE ABSTRACT Myostatin (MSTN) is a negative regulator during muscle differentiation, whereas insulin-like growth factors (IGFs) are essential for muscle development. MSTN and IGFs act oppositely during myogenesis, but there is little information on the mutual relationship of MSTN and IGFs. The present study was conducted to examine whether MSTN affects IGF expression during early myogenesis in cattle. IGF-1 mRNA was similarly expressed in M. longissimus thoracis of double-muscled (DM) and normal (NM) Japanese shorthorn cattle. IGF-2 mRNA expression was consistently higher in the normal and regenerating muscle of DM cattle than those of NM cattle. When myoblasts were isolated from regenerating M. longissimus thoracis, IGF-2 mRNA expression showed a significant increase in differentiating DM derived myoblasts (DM-myoblasts) as compared with differentiating NM derived myoblasts (NM-myoblasts). An addition of recombinant mouse myostatin (rMSTN) to myoblast cultures attenuated IGF-2 mRNA expression and decreased myotube formation, but did not effect IGF-1 mRNA expression. An activin-like kinase (ALK) inhibitor, SB431542, mediates MSTN action, suppressed the translocation of Smad2/3 into the nucleus in DM-myoblasts, and restored the attenuated IGF-2 mRNA expression and the decreased myotube formation induced by rMSTN in myoblast cultures. The findings indicate that MSTN may negatively regulate myoblast differentiation by suppressing IGF-2 expression via ALK-Smad signaling. [source] | ||||||||||||||||||||||||||||