FGF receptor availability regulates skeletal myogenesis.
Fibroblast growth factors (FGFs) and their receptors are critical participants in embryonic development, including the genesis of skeletal, cardiac, and smooth muscle. FGF signaling is mediated through interactions between multiple FGF ligands and transmembrane tyrosine kinase receptors, resulting in activation of a number of signal transduction pathways. Skeletal myocytes express FGF ligands and receptors in a coordinated fashion, suggesting that these molecules participate in autocrine signaling in the myocyte. Endogenously produced FGF has been shown to inhibit myogenesis, but the role of FGF receptor availability in directing myocyte proliferation and differentiation has not been established. To determine the contribution of receptor availability to the regulation of myogenesis, receptor availability was either increased by expressing a full-length FGF receptor-1 or decreased by expressing a truncated FGF receptor-1 in cultured skeletal myocytes. Constitutive expression of a full-length FGF receptor-1 increased myocyte proliferation and delayed differentiation. Conversely, a reduction in functional FGF receptor signaling by expression of a truncated FGF receptor-1 decreased proliferation and enhanced differentiation of myocytes. These data demonstrate that FGF receptor availability plays a critical regulatory role in skeletal myogenesis.
Scata
K A
KA
Cell and Molecular Biology Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
Bernard
D W
DW
Fox
J
J
Swain
J L
JL
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D008024:Ligands; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; C496349:Fgfr1 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1