Induction of cardiac muscle differentiation in isolated animal pole explants of Xenopus laevis embryos

Development ◽  
1993 ◽  
Vol 118 (3) ◽  
pp. 865-875 ◽  
Author(s):  
M. Logan ◽  
T. Mohun
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Xenopus Laevis ◽  
Cardiac Muscle ◽  
Muscle Differentiation ◽  
Specific Marker ◽  
Skeletal Muscle Differentiation ◽  
Animal Pole ◽  
Alpha Gene

We have isolated a cDNA fragment encoding a portion of the myosin heavy chain alpha-isoform (XMHC alpha) in the amphibian, Xenopus laevis. The XMHC alpha transcript is highly enriched in adult heart RNA and is expressed exclusively in embryonic heart tissue. It therefore provides a tissue-specific marker for cardiac muscle differentiation during early embryogenesis. Using an RNAase protection assay, we can detect the onset of cardiac muscle differentiation in an anterior, ventral region of tailbud embryos, many hours before the appearance of a beating heart. Whole-mount in situ RNA hybridisation indicates that expression of the XMHC alpha gene is restricted to the developing heart primordium. XMHC alpha gene expression can also be induced in isolated animal pole explants of blastulae by treatment with the growth factor, activin A. Induction is dose-dependent, requiring high doses of the growth factor compared with that required for myotomal (skeletal) muscle differentiation. In contrast, no XMHC alpha transcripts are detected in explants incubated with basic FGF, despite the induction of myotomal muscle differentiation. Activin-induced explants show a similar temporal pattern of XMHC alpha gene expression to that found in normal embryogenesis. Furthermore, cells expressing this gene appear clustered in one or two foci within fused explant aggregates, which often show regular, spontaneous contractions after several days in culture. These results show that terminal differentiation of cardiac muscle can occur in growth factor-induced explants and may be distinguished from skeletal muscle differentiation by the dose and nature of the inducing factor.

scholarly journals Sarcosin (Krp1) in skeletal muscle differentiation: gene expression profiling and knockdown experiments

2012 ◽  
Vol 56 (4) ◽  
pp. 301-309 ◽  
Author(s):  
Leonie Du Puy ◽  
Abdelaziz Beqqali ◽  
Helena T.A. Van Tol ◽  
Jantine Monshouwer-Kloots ◽  
Robert Passier ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Muscle Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Differentiation Gene

scholarly journals MyoD inhibits Fstl1 and Utrn expression by inducing transcription of miR-206

2006 ◽  
Vol 175 (1) ◽  
pp. 77-85 ◽  
Author(s):  
Miriam I. Rosenberg ◽  
Sara A. Georges ◽  
Amy Asawachaicharn ◽  
Erwin Analau ◽  
Stephen J. Tapscott
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Transcriptional Activation ◽  
Cell Types ◽  
Muscle Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Distinct Cell ◽  
Muscle Genes ◽  
Suppression Of Gene Expression ◽  
Dystrophin Protein

Terminal differentiation of distinct cell types requires the transcriptional activation of differentiation-specific genes and the suppression of genes associated with the precursor cell. For example, the expression of utrophin (Utrn) is suppressed during skeletal muscle differentiation, and it is replaced at the sarcolemma by the related dystrophin protein. The MyoD transcription factor directly activates the expression of a large number of skeletal muscle genes, but also suppresses the expression of many genes. To characterize a mechanism of MyoD-mediated suppression of gene expression, we investigated two genes that are suppressed in fibroblasts converted to skeletal muscle by MyoD, follistatin-like 1 (Fstl1) and Utrn. MyoD directly activates the expression of a muscle-specific microRNA (miRNA), miR-206, which targets sequences in the Fstl1 and Utrn RNA, and these sequences are sufficient to suppress gene expression in the presence of miR-206. These findings demonstrate that MyoD, in addition to activating muscle-specific genes, induces miRNAs that repress gene expression during skeletal muscle differentiation.

scholarly journals A Novel Mechanism of Sequestering Fibroblast Growth Factor 2 by Glypican in Lipid Rafts, Allowing Skeletal Muscle Differentiation

2010 ◽  
Vol 30 (7) ◽  
pp. 1634-1649 ◽  
Author(s):  
Jaime Gutiérrez ◽  
Enrique Brandan
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Lipid Rafts ◽  
Muscle Differentiation ◽  
Myoblast Fusion ◽  
Fibroblast Growth Factor 2 ◽  
Skeletal Muscle Differentiation ◽  
Fibroblast Growth ◽  
Raft Domains

ABSTRACT Heparan sulfate proteoglycans (HSPGs) are critical modulators of growth factor activities. Skeletal muscle differentiation is strongly inhibited by fibroblast growth factor 2 (FGF-2). We have shown that HSPGs present at the plasma membrane are expressed in myoblasts and are downregulated during muscle differentiation. An exception is glypican-1, which is present throughout the myogenic process. Myoblasts that do not express glypican-1 exhibit defective differentiation, with an increase in the receptor binding of FGF-2, concomitant with increased signaling. Glypican-1-deficient myoblasts show decreased expression of myogenin, the master gene that controls myogenesis, myosin, and the myoblast fusion index. Reversion of these defects was induced by expression of rat glypican-1. Glypican-1 is the only HSPG localized in lipid raft domains in myoblasts, resulting in the sequestration of FGF-2 away from FGF-2 receptors (FGFRs) located in nonraft domains. A chimeric glypican-1, containing syndecan-1 transmembrane and cytoplasmic domains, is located in nonraft domains interacting with FGFR-IV- and enhanced FGF-2-dependent signaling. Thus, glypican-1 acts as a positive regulator of muscle differentiation by sequestering FGF-2 in lipid rafts and preventing its binding and dependent signaling.

scholarly journals A requirement for fibroblast growth factor in regulation of skeletal muscle growth and differentiation cannot be replaced by activation of platelet-derived growth factor signaling pathways.

1995 ◽  
Vol 15 (6) ◽  
pp. 3238-3246 ◽  
Author(s):  
A J Kudla ◽  
M L John ◽  
D F Bowen-Pope ◽  
B Rainish ◽  
B B Olwin
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Map Kinase ◽  
Signaling Pathways ◽  
Receptor Tyrosine Kinase ◽  
Muscle Differentiation ◽  
Receptor Activation ◽  
Skeletal Muscle Differentiation ◽  
Fgf Receptor ◽  
Beta Receptor

The distinct effects of cytokines on cellular growth and differentiation suggest that specific signaling pathways mediate these diverse biological activities. Fibroblast growth factors (FGFs) are well-established inhibitors of skeletal muscle differentiation and may operate via activation of specific signaling pathways distinct from recently identified mitogen signaling pathways. We examined whether platelet-derived growth factor (PDGF)-activated signaling pathways are sufficient to mediate FGF-dependent repression of myogenesis by introducing the PDGF beta receptor into a mouse skeletal muscle cell line. Addition of PDGF-BB to cells expressing the PDGF beta receptor activated the PDGF beta receptor tyrosine kinase, stimulated mitogen-activated protein (MAP) kinase, and increased the steady-state levels of junB and c-fos mRNAs. Despite the activation of these intracellular signaling molecules, PDGF beta receptor activation elicited no detectable effect on cell proliferation or differentiation. In contrast to PDGF-BB, addition of FGF-2 to myoblasts activated signaling pathways that resulted in DNA synthesis and repression of differentiation. Because of the low number of endogenous FGF receptors expressed, FGF-stimulated signaling events, including tyrosine phosphorylation and activation of MAP kinase, could be detected only in cells expressing higher levels of a transfected FGF receptor cDNA. As the PDGF beta receptor- and FGF receptor-stimulated signaling pathways yield different biological responses in these skeletal muscle cells, we hypothesize that FGF-mediated repression of skeletal muscle differentiation activates signaling pathways distinct from those activated by the PDGF beta receptor. Activation of PDGF beta receptor tyrosine kinase activity, stimulation of MAP kinase, and upregulation of immediate-early gene expression are not sufficient to repress skeletal muscle differentiation.

scholarly journals Coordinated Vascular Endothelial Growth Factor Expression and Signaling During Skeletal Myogenic Differentiation

2008 ◽  
Vol 19 (3) ◽  
pp. 994-1006 ◽  
Author(s):  
Brad A. Bryan ◽  
Tony E. Walshe ◽  
Dianne C. Mitchell ◽  
Josh S. Havumaki ◽  
Magali Saint-Geniez ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Myogenic Differentiation ◽  
Es Cells ◽  
Muscle Differentiation ◽  
C2c12 Cells ◽  
Vascular Endothelial ◽  
Skeletal Muscle Differentiation ◽  
Endothelial Growth Factor

Angiogenesis is largely controlled by hypoxia-driven transcriptional up-regulation and secretion of vascular endothelial growth factor (VEGF) and its binding to the endothelial cell tyrosine receptor kinases, VEGFR1 and VEGFR2. Recent expression analysis suggests that VEGF is expressed in a cell-specific manner in normoxic adult tissue; however, the transcriptional regulation and role of VEGF in these tissues remains fundamentally unknown. In this report we demonstrate that VEGF is coordinately up-regulated during terminal skeletal muscle differentiation. We reveal that this regulation is mediated in part by MyoD homo- and hetero-dimeric transcriptional mechanisms. Serial deletions of the VEGF promoter elucidated a region containing three tandem CANNTG consensus MyoD sites serving as essential sites of direct interaction for MyoD-mediated up-regulation of VEGF transcription. VEGF-null embryonic stem (ES) cells exhibited reduced myogenic differentiation compared with wild-type ES cells, suggesting that VEGF may serve a role in skeletal muscle differentiation. We demonstrate that VEGFR1 and VEGFR2 are expressed at low levels in myogenic precursor cells and are robustly activated upon VEGF stimulation and that their expression is coordinately regulated during skeletal muscle differentiation. VEGF stimulation of differentiating C2C12 cells promoted myotube hypertrophy and increased myogenic differentiation, whereas addition of sFlt1, a VEGF inhibitor, resulted in myotube hypotrophy and inhibited myogenic differentiation. We further provide evidence indicating VEGF-mediated myogenic marker expression, mitogenic activity, migration, and prosurvival functions may contribute to increased myogenesis. These data suggest a novel mechanism whereby VEGF is coordinately regulated as part of the myogenic differentiation program and serves an autocrine function regulating skeletal myogenesis.

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