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PubMed1989

Insulin-like growth factors (IGF) in muscle development. Expression of IGF-I, the IGF-I receptor, and an IGF binding protein during myoblast differentiation.

The insulin-like growth factors (IGFs) I and II exert pleiotropic effects on diverse cell types through interaction with specific high affinity cell surface receptors and with locally produced binding proteins. In skeletal muscle and in myoblast cell lines, the functions of IGF-I and -II are complex. Both growth factors appear capable of stimulating cellular proliferation and differentiation, as well as exerting insulin-like effects on intermediary metabolism. We have demonstrated recently that the expression of IGF-II and its receptor is induced during the terminal differentiation of the myoblast cell line, C2, and have suggested that IGF-II may be an autocrine growth factor in these cells (Tollefsen, S.E., Sadow, J.L., and Rotwein, P. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 1543-1547). We now have examined this cell line for expression of other components involved in IGF signaling. The synthesis of IGF-I is low during myoblast proliferation; IGF-I mRNA can be detected only through use of a sensitive solution hybridization assay. Typical IGF-I receptors can be measured in myoblasts, whereas IGF binding proteins cannot be detected in proliferating cells or in conditioned culture medium. During myogenic differentiation, IGF-I mRNA levels increase transiently by 6-10-fold within 48-72 h. The expression of IGF-I mRNA is accompanied by a 2.5-fold accumulation of IGF-I in the culture medium. IGF-I receptors also increase transiently, doubling by 48 h after the onset of differentiation. By contrast, secretion of a Mr 29,000 IGF binding protein is induced 30-fold to 100 ng/ml within 16 h and continues to increase throughout differentiation. These studies demonstrate that several components critical to IGF action are produced in a fusing skeletal muscle cell line in a differentiation-dependent manner and suggest that both IGF-I and IGF-II may be autocrine factors for muscle.

Amino Acid Sequence↗
PubMed1985

Human glyceraldehyde-3-phosphate dehydrogenase: mRNA levels and enzyme activity in developing muscle.

Analysis of human glyceraldehyde-3-phosphate dehydrogenase mRNA revealed that levels in adult skeletal muscle are 12-fold greater per microgram of polyadenylated RNA than in fetal skeletal muscle, whereas in cardiac muscle RNA levels were about equal in fetal and adult tissue. The mRNA levels correlate well with glyceraldehyde 3-phosphate dehydrogenase enzyme activities. There was no evidence for fetus- or tissue-specific forms.

Adult↗
PubMed1998

Distinct molecular phenotypes in murine cardiac muscle development, growth, and hypertrophy.

The onset of cardiac hypertrophy is associated with characteristic changes in myocardial gene expression that are thought to recapitulate a developmental gene program. We report here the first gene expression profile of the murine myocardium, using a rapid method of quantitative expression analysis based on real-time analytical RT-PCR. This assay was used to measure expression levels of 29 genes in (1) late stage development as represented by day 1 neonatal ventricles, (2) normal cardiac growth in 3 and 18 month old mice, and (3) cardiac hypertrophy following pressure overload by aortic constriction. For males and females normal growth is not associated with differential expression although there is elevated expression of skeletal and smooth muscle actin mRNA's in males compared to females. Using normal adult ventricles as a reference, there are many qualitative and quantitative differences between the day 1 neonatal myocardium and experimental cardiac hypertrophy. These data suggest that the response to POL involves a subset of re-expressed developmental genes together with altered expression of genes not necessarily associated with cardiac development.

Animals↗
PubMed1993

Ultrastructure of the developing muscle and enteric nervous system in the small intestine of human fetus.

The ultrastructural organization and some histochemical characteristics of the enteric nervous system (ENS) were investigated in 10- and 18-week-old human fetuses. In the 10-week-old human fetus immature myoblasts, and mostly neuroblasts were found in the ganglia. Simple, undifferentiated neuropil was observed among neuronal cells. The neuropil generally did not contain synapses; however axosomatic synapse was registered rarely on the surface of certain neurons. Neuromuscular junctions were common, both axons and neurons were in close contact with the sarcolemma. In the 18-week-old human fetus the fine-structural characteristics of the intestinal smooth muscle cells were the same as in the adult. Nerve profiles were frequently found among the muscle cells. NADH-diaphorase histochemistry revealed the presence of numerous ganglia but solitary neurons still occurred. Differentiated neurons and neuroblasts could be distinguished in the myenteric ganglia. Synapses were often detected in the neuropil. Thick nerve plexuses were frequently found in the proximity of smooth muscle cells, forming "distant" and "close" myoneural contacts. Well-defined fluorescent network and several fluorescent nerve cell bodies were demonstrated by glyoxylic acid. The above organization may provide a satisfactory basis for an integrated peristaltic movement in the gut of the 18-week-old human fetus.

Axons↗
PubMed1996

Specific localization of zebrafish hsp90 alpha mRNA to myoD-expressing cells suggests a role for hsp90 alpha during normal muscle development.

Members of the eukaryotic hsp90 family function as important molecular chaperones in the assembly, folding and activation of a select group of cellular signalling molecules and transcription factors. Several of the molecules with which hsp90 interacts, such as the bHLH transcription factor myoD, are known to be important regulators of developmental events in vertebrates. However, little information is available in support of any specific role for hsp90 in developing embryos in vivo. In this study, we provide the first in vivo evidence that the hsp90 alpha gene may play a role in the process of myogenesis. We show that constitutive hsp90 alpha mRNA in zebrafish embryos is restricted primarily to a subset of cells within the somites and pectoral fin buds which also express myoD. Furthermore, expression of the hsp90 alpha gene is down-regulated along with myoD in differentiated muscles of the trunk at a time when levels of mRNA encoding the muscle structural protein alpha-tropomyosin remain high. No hsp90 alpha mRNA is detectable within the CNS at control temperatures. In contrast, heat shock-induced expression of the hsp90 alpha gene occurs throughout the embryo at all stages of development examined. The expression patterns strongly suggest that the hsp90 alpha gene plays a specific role in the normal process of myogenesis in addition to providing protection to all cells of the embryo during periods of environmental stress.

Animals↗
PubMed1998

Integrins during muscle development and in muscular dystrophies.

Cellular interactions with the extracellular matrix (ECM) have been shown to be important for a number of developmental events from the time of fertilization up till the maturation of the organism. In the following review we will discuss what is currently known about these interactions with special emphasis on the role of integrins during the formation of skeletal muscle. The importance of cell-ECM interactions will also be illustrated by a discussion of what happens when these interactions go awry, as happens in muscular dystrophies.

Animals↗
PubMed1992

Actions of thrombin and thrombin receptor peptide analogues in gastric and aortic smooth muscle: development of bioassays for structure-activity studies.

We have examined the biological activities of thrombin and the thrombin-receptor-related polypeptides, S42FLLRNPNDKYEPF55(TRP42-55), S42FLLRNPND50(TRP42-50), and A42FLLRNPND50(A42-TRP42-50) as well as an arginine-containing basic peptide beginning with the SF motif (SFRGHITR), in rat aortic (RA) rings and in a gastric guinea pig longitudinal (LM) smooth muscle preparation. In the RA preparation, thrombin, as well as the three receptor-related peptides caused a relaxation in tissue that was precontracted with noradrenaline; the basic peptide, SFRGHITR, was inactive either as an agonist or as an antagonist to TRP42-55. In the LM bioassay, which unlike the RA preparation did not persistently desensitize in response to thrombin, all three receptor-related peptides, like thrombin, caused a prompt phasic reproducible contraction. The basic peptide, SFRGHITR, was inactive. In the LM assay, TRP42-55, TRP42-50 and A42-TRP42-55 all caused comparable contractile responses. We conclude that the gastric LM smooth muscle possesses a thrombin receptor and provides a convenient and reliable assay for the activities of thrombin receptor-related peptides. Our data also demonstrated that neither the C-terminal hirudin-related pentapeptide nor the N-terminal serine hydroxyl group are required for the biological activity of the thrombin receptor-derived peptide previously described (TRP42-55). Based on our findings we suggest that only a small portion of the N-terminal sequence of TRP42-55 may be required for thrombin-like biological activity.

Amino Acid Sequence↗
PubMed2004

Integrating transcriptional and signalling networks during muscle development.

A fundamental aspect of developmental decisions is the ability of groups of cells to obtain the competence to respond to different signalling inputs. This information is often integrated with intrinsic transcriptional networks to produce diverse developmental outcomes. Studies in Drosophila are starting to reveal a detailed picture of the regulatory circuits controlling the subdivision of the dorsal mesoderm, which gives rise to diverse muscle types including cardioblasts, pericardial cells, body wall muscle and gut muscle. The combination of a common set of mesoderm autonomous transcription factors (e.g. Tinman and Twist) and spatially restricted inductive signals (e.g. Dpp and Wg) subdivide the dorsal mesoderm into different competence domains. The integration of additional signalling inputs with localised repression within these competence domains results in diverse transcriptional responses within neighbouring cells, which in turn generates muscle diversity.

Animals↗
PubMed2001

Muscle development: reversal of the differentiated state.

Cell fate selection and cell cycle exit are fundamental features of differentiation during animal development. Accumulating data suggest that these processes are more readily reversible than previously supposed and are beginning to point at the underlying molecular mechanisms.

Animals↗
PubMed1999

Cardiac and skeletal muscle development in P19 embryonal carcinoma cells.

Mouse P19 embryonal carcinoma cells are pluripotent stem cells that can be maintained in culture in an undifferentiated state or can be induced to differentiate in vitro into multiple cell types. P19 cells aggregated in the presence of dimethylsulfoxide differentiate into spontaneously beating cardiomyocytes and bipolar skeletal myocytes that exhibit the biochemical and physiologic properties of their embryonic equivalents. P19 cells can be readily manipulated genetically, resulting in the loss or over-expression of a gene of interest. Because of this versatility, the P19 system is suited for examining the molecular mechanisms controlling the developmental decisions of stem cells differentiating into the skeletal or cardiac muscle lineage.

Animals↗