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

Analysis of MM14 mouse myoblasts demonstrates that terminal differentiation is repressed by pure preparations of both acidic and basic fibroblast growth factor (FGF). Basic FGF is approximately 30-fold more potent than acidic FGF and it exhibits half maximal activity in clonal assays at 0.03 ng/ml (2 pM). FGF repression occurs only during the G1 phase of the cell cycle by a mechanism that appears to be independent of ongoing cell proliferation. When exponentially growing myoblasts are deprived of FGF, cells become postmitotic within 2-3 h, express muscle-specific proteins within 6-7 h, and commence fusion within 12-14 h. Although expression of these three terminal differentiation phenotypes occurs at different times, all are initiated by a single regulatory "commitment" event in G1. The entire population commits to terminal differentiation within 12.5 h of FGF removal as all cells complete the cell cycle and move into G1. Differentiation does not require a new round of DNA synthesis. Comparison of MM14 behavior with other myoblast types suggests a general model for skeletal muscle development in which specific growth factors serve the dual role of stimulating myoblast proliferation and directly repressing terminal differentiation.

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Expression of fibroblast growth factor 2 and its receptor during skeletal muscle development from turkeys with different growth rates

Domestic Animal Endocrinology ◽

10.1016/s0739-7240(03)00061-4 ◽

2003 ◽

Vol 25 (2) ◽

pp. 215-229 ◽

Cited By ~ 10

Author(s):

X. Liu ◽

D.C. McFarland ◽

K.E. Nestor ◽

S.G. Velleman

Keyword(s):

Skeletal Muscle ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Growth Rates ◽

Muscle Development ◽

Fibroblast Growth Factor 2 ◽

Fibroblast Growth ◽

Skeletal Muscle Development

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Murine cortactin is phosphorylated in response to fibroblast growth factor-1 on tyrosine residues late in the G1 phase of the BALB/c 3T3 cell cycle.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(20)80543-2 ◽

1993 ◽

Vol 268 (32) ◽

pp. 24427-24431

Author(s):

X Zhan ◽

X Hu ◽

B Hampton ◽

W.H. Burgess ◽

R Friesel ◽

...

Keyword(s):

Cell Cycle ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

G1 Phase ◽

Fibroblast Growth ◽

Tyrosine Residues

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Control of myogenic differentiation by fibroblast growth factor is mediated by position in the G1 phase of the cell cycle.

The Journal of Cell Biology ◽

10.1083/jcb.101.6.2194 ◽

1985 ◽

Vol 101 (6) ◽

pp. 2194-2198 ◽

Cited By ~ 63

Author(s):

B Lathrop ◽

K Thomas ◽

L Glaser

Keyword(s):

Cell Cycle ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Myogenic Differentiation ◽

G1 Phase ◽

Primary Control ◽

Fibroblast Growth ◽

Restriction Point ◽

Polypeptide Growth Factors ◽

Specific Proteins

We have used the expression of the muscle form of creatine phosphokinase (M-CPK) to assay myogenic differentiation in the cloned muscle cell line BC3Hl. BC3Hl cells express M-CPK when arrested in the G0 portion of the cell cycle. Addition of the anionic form of brain fibroblast growth factor (B-FGF) rapidly represses synthesis of M-CPK with a half-time of 7 h. Even though B-FGF is not mitogenic for the cells, it causes quiescent BC3Hl cells to exit from the G0 portion of the cell cycle, and to accumulate at a new restriction point approximately 4 to 6 h in the G1 portion of the cell cycle. The repression of M-CPK synthesis by B-FGF is reversible upon removal of B-FGF, and cells which have re-initiated expression of M-CPK have also returned to the G0 portion of the cell cycle. The primary control of M-CPK expression by B-FGF appears to be at the level of gene transcription. We conclude that arrest of cells at G0 but not at other positions in the G1 phase of the cell cycle provides permissive conditions for the expression of muscle-specific proteins, and that defined polypeptide growth factors, in this case B-FGF, are important in the control of the expression of muscle-specific proteins.

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Faculty Opinions recommendation of Fibroblast growth factor 19 regulates skeletal muscle mass and ameliorates muscle wasting in mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727746955.793533652 ◽

2017 ◽

Author(s):

Sakae Tanaka

Keyword(s):

Skeletal Muscle ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Muscle Wasting ◽

Fibroblast Growth ◽

Fibroblast Growth Factor 19

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Gait disturbances and muscle dysfunction in fibroblast growth factor 2 knockout mice

Scientific Reports ◽

10.1038/s41598-021-90565-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

C. Homer-Bouthiette ◽

L. Xiao ◽

Marja M. Hurley

Keyword(s):

Skeletal Muscle ◽

Growth Factor ◽

Muscle Strength ◽

Fibroblast Growth Factor ◽

Muscle Function ◽

Fibroblast Growth Factor 2 ◽

Fibroblast Growth ◽

Skeletal Muscle Function ◽

Age Related ◽

Gait Disturbances

AbstractFibroblast growth factor 2 (FGF2) is important in musculoskeletal homeostasis, therefore the impact of reduction or Fgf2 knockout on skeletal muscle function and phenotype was determined. Gait analysis as well as muscle strength testing in young and old WT and Fgf2KO demonstrated age-related gait disturbances and reduction in muscle strength that were exacerbated in the KO condition. Fgf2 mRNA and protein were significantly decreased in skeletal muscle of old WT compared with young WT. Muscle fiber cross-sectional area was significantly reduced with increased fibrosis and inflammatory infiltrates in old WT and Fgf2KO vs. young WT. Inflammatory cells were further significantly increased in old Fgf2KO compared with old WT. Lipid-related genes and intramuscular fat was increased in old WT and old Fgf2KO with a further increase in fibro-adipocytes in old Fgf2KO compared with old WT. Impaired FGF signaling including Increased β-Klotho, Fgf21 mRNA, FGF21 protein, phosphorylated FGF receptors 1 and 3, was observed in old WT and old Fgf2KO. MAPK/ ERK1/2 was significantly increased in young and old Fgf2KO. We conclude that Fgf2KO, age-related decreased FGF2 in WT mice, and increased FGF21 in the setting of impaired Fgf2 expression likely contribute to impaired skeletal muscle function and sarcopenia in mice.

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