Growth factor control of skeletal muscle differentiation: commitment to terminal differentiation occurs in G1 phase and is repressed by fibroblast growth factor.

Clegg, Christopher H.; Linkhart, Thomas A.; Olwin, Bradley B.; Hauschka, Stephen D.

doi:10.1083/jcb.105.2.949

Cited by 454 publications

(315 citation statements)

References 38 publications

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“…The inhibition of di erentiation by FGF-2, IGF-1, TGFb, or oncogenic Ras relies on continual signaling (Lathrop et al, 1985;Olson et al, 1986;Clegg et al, 1987;Gossett et al, 1988;Vaidya et al, 1989;Nakafuku et al, 1992). Induction of an autocrine loop would be an e cient mechanism to ensure a continual supply of inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Oncogenic Ras-induced secretion of a novel inhibitor of skeletal myoblast differentiation

Weyman

Wolfman

1997

Oncogene

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Expression of oncogenic H-Ras in 23A2 myoblasts (A2:H-Ras cells) is su cient to induce both a transformed phenotype and a di erentiation-defective phenotype. Because oncogenic Ras is known to induce the secretion of several di erent growth factors involved in maintaining the transformed phenotype of both ®broblast and epithelial cells, we explored the possibility that expression of oncogenic Ras in 23A2 myoblasts might lead to the secretion of a factor which inhibits di erentiation. The di erentiation of 23A2 myoblasts was inhibited (i) by coculture with an equal number of A2:H-Ras cells, (ii) by culture with an equal number of A2:H-Ras cells in the same tissue culture medium on an insert which allowed equilibration of molecules smaller than 1 micron, and (iii) by culture in media previously conditioned by A2:H-Ras cells. Similar results were obtained when 23A2 myoblasts expressing oncogenic NRas were substituted for A2:H-Ras cells in each assay. No inhibition of di erentiation was observed, however, when di erentiation-defective E1A-expressing 23A2 cells or C3H10T1/2 ®broblasts were substituted for A2:HRas cells. The di erentiation inhibitor(s) in media conditioned by A2:H-Ras cells is heat stable, larger than 3 kD, and sensitive to the non-speci®c growth factor antagonist, suramin. Western analyses failed to detect either FGF-2 or TGFb (the known inhibitors of myoblast di erentiation) in media conditioned by A2:H-Ras cells. Furthermore, while FGF-2 is a potent activator of MAP kinase and TGFb is a potent inhibitor of mink lung epithelial cell (CCL64) growth, conditioned media from A2:H-Ras cells does not activate MAP kinase and does not inhibit the growth of CCL64 cells. These results indicate that expression of oncogenic Ras induces the secretion of a novel inhibitor of skeletal myoblast di erentiation. Furthermore, these results are the ®rst to implicate an autocrine/paracrine mechanism in the inhibition of di erentiation by oncogenic Ras.

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Section: Discussionmentioning

confidence: 99%

Oncogenic Ras-induced secretion of a novel inhibitor of skeletal myoblast differentiation

Weyman

Wolfman

1997

Oncogene

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“…When myoblasts are placed in tissue culture, their differentiation is repressed by high concentrations of serum. FGF is one of the most potent inhibitors of murine cell myogenesis in vitro (Clegg et al, 1987). Myogenic differentiation is similarly repressed by high serum concentrations in newt blastema cells in vitro (Ferretti and Brockes, 1988;Casimir et al, 1988;Lo et al, 1993).…”

Section: T T T a C T T A A G T C A T T T G G T T G G C A C A C A T A mentioning

confidence: 99%

Differential expression of myogenic regulatory genes and Msx‐1 during dedifferentiation and redifferentiation of regenerating amphibian limbs

Simon

Nelson

Goff

et al. 1995

Developmental Dynamics

110

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An amputated limb of an adult urodele amphibian is capable of undergoing regeneration. The new structures form from an undifferentiated mass of cells called the regenerative blastema. The cells of the blastema are believed to derive from differentiated tissues of the adult limb. However, the exact source of these cells and the process by which they undergo dedifferentiation are poorly understood. In order to elucidate the molecular and cellular basis for dedifferentiation we isolated a number of genes which are potential regulators of the process. These include Msx‐1, which is believed to support the undifferentiated and proliferative state of cells in the embryonic limb bud; and two members of the myogenic regulatory gene family, MRF‐4 and Myf‐5, which are expressed in differentiated muscle and regulate muscle‐specific gene activity. As anticipated, we find that Msx‐1 is strongly up‐regulated during the initiation of regeneration. It remains expressed throughout regeneration but is not found in the fully regenerated limb. The myogenic gene MRF‐4 has the reverse expression pattern. It is expressed in adult limb muscle, is rapidly shut off in early regenerative blastemas, and is only reexpressed at the completion of regeneration. These kinetics are paralleled by those of a musclespecific Myosin gene. In contrast Myf‐5, a second member of the myogenic gene family, continues to be expressed throughout the regenerative process. Thus, MRF‐4 and Myf‐5 are likely to play distinct roles during regeneration. MRF‐4 may directly regulate muscle phenotype and as such its repression may be a key event in dedifferentiation. Myf‐5 may play a role in maintaining a distinct myogenic lineage during regeneration. © 1995 Wiley‐Liss, Inc.

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“…MM14 myoblasts [23,24] were amplified in culture under growth conditions, which for this satellite cell-derived line includes addition of supplementary FGF-2 every 12 hours to prevent commitment to terminal differentiation during the G1 phase of the cell cycle. To produce a heterogeneous population of proliferating and recently-committed cells, cultures that had previously been supplemented with FGF-2 were not given additional FGF-2 for 12 hrs, leading to depletion of the available FGF2 and subsequent commitment of a fraction of the cells to differentiation.…”

Section: Fluorescence-activated Cell Sorting Analysismentioning

confidence: 99%

“…MM14s are a satellite cell-derived cell line with morphology and gene expression very similar to primary satellite cells [23,66]. They are dependent on FGF2 stimulation during the G1 phase of the cell cycle to prevent commitment to terminal differentiation [24]. The cells were amplified in culture under growth conditions then deprived of additional FGF2 for 12 hours before staining and sorting (Fig.…”

Section: Facs Sorting Of Ncam +Ve and Ncam −Ve Cellsmentioning

confidence: 99%

Neural cell adhesion molecule (NCAM) marks adult myogenic cells committed to differentiation

Capkovic

Stevenson

Johnson

et al. 2008

Experimental Cell Research

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Although recent advances in broad-scale gene expression analysis have dramatically increased our knowledge of the repertoire of mRNAs present in multiple cell types, it has become increasingly clear that examination of the expression, localization, and associations of the encoded proteins will be critical for determining their functional significance. In particular, many signaling receptors, transducers, and effectors have been proposed to act in higher-order complexes associated with physically distinct areas of the plasma membrane. Adult muscle stem cells (satellite cells) must, upon injury, respond appropriately to a wide range of extracellular stimuli: the role of such signaling scaffolds is therefore a potentially important area of inquiry. To address this question, we first isolated detergent-resistant membrane fractions from primary satellite cells, then analyzed their component proteins using liquid chromatography-tandem mass spectrometry. Transmembrane and juxtamembrane components of adhesion-mediated signaling pathways made up the largest group of identified proteins; in particular, neural cell adhesion molecule (NCAM), a multifunctional cell-surface protein that has previously been associated with muscle regeneration, was significant. Immunohistochemical analysis revealed that not only is NCAM localized to discrete areas of the plasma membrane, it is also a very early marker of commitment to terminal differentiation. Using flow cytometry, we have sorted physically homogeneous myogenic cultures into proliferating and differentiating fractions based solely upon NCAM expression.

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Growth factor control of skeletal muscle differentiation: commitment to terminal differentiation occurs in G1 phase and is repressed by fibroblast growth factor.

Cited by 454 publications

References 38 publications

Oncogenic Ras-induced secretion of a novel inhibitor of skeletal myoblast differentiation

Oncogenic Ras-induced secretion of a novel inhibitor of skeletal myoblast differentiation

Differential expression of myogenic regulatory genes and Msx‐1 during dedifferentiation and redifferentiation of regenerating amphibian limbs

Neural cell adhesion molecule (NCAM) marks adult myogenic cells committed to differentiation

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