FGFR4 signaling is a necessary step in limb muscle differentiation.
In chick embryos, most if not all, replicating myoblasts present within the skeletal muscle masses express high levels of the FGF receptor FREK/FGFR4, suggesting an important role for this molecule during myogenesis. We examined FGFR4 function during myogenesis, and we demonstrate that inhibition of FGFR4, but not FGFR1 signaling, leads to a dramatic loss of limb muscles. All muscle markers analyzed (such as Myf5, MyoD and the embryonic myosin heavy chain) are affected. We show that inhibition of FGFR4 signal results in an arrest of muscle progenitor differentiation, which can be rapidly reverted by the addition of exogenous FGF, rather than a modification in their proliferative capacities. Conversely, over-expression of FGF8 in somites promotes FGFR4 expression and muscle differentiation in this tissue. Together, these results demonstrate that in vivo, myogenic differentiation is positively controlled by FGF signaling, a notion that contrasts with the general view that FGF promotes myoblast proliferation and represses myogenic differentiation. Our data assign a novel role to FGF8 during chick myogenesis and demonstrate that FGFR4 signaling is a crucial step in the cascade of molecular events leading to terminal muscle differentiation.
Marics
Irène
I
Developmental Biology Institute of Marseille, Laboratoire de Génétique et de Physiologie du Développement (LGPD), University Aix-Marseille II, Campus de Luminy, Case 907, 13288 Marseille Cedex 09, France.
Padilla
Françoise
F
Guillemot
Jean-François
JF
Scaal
Martin
M
Marcelle
Christophe
C
D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation; D002455:Cell Division; D002642:Chick Embryo; D004268:DNA-Binding Proteins; D005121:Extremities; D015870:Gene Expression; D018878:Limb Buds; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics; D051787:Myogenic Regulatory Factor 5; D018995:Myosin Heavy Chains / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051499:Receptor, Fibroblast Growth Factor, Type 4; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D015534:Trans-Activators; D029867:Xenopus Proteins; D014982:Xenopus laevis
D015415:Biomarkers; D004268:DNA-Binding Proteins; D009124:Muscle Proteins; C497419:Myf5 protein, Xenopus; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D029867:Xenopus Proteins; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051499:Receptor, Fibroblast Growth Factor, Type 4; D018995:Myosin Heavy Chains