Loss of fibroblast growth factor receptors is necessary for terminal differentiation of embryonic limb muscle.

Early in embryogenesis, precursors of the limb musculature are generated in the somite, migrate to the limb buds and undergo terminal differentiation. Although myogenic differentiation in culture is affected by several growth factors including fibroblast growth factor (FGF), it remains uncertain whether migration and differentiation of myogenic cells in vivo are directly regulated by such growth factors. To investigate the roles of FGF signaling in the regulation of myogenesis both in the somite and the limb bud, mosaic chicken embryos were generated that consist of somitic cells carrying transgenes expressing one of the following: FGF1, FGF4, the FGF receptor type-1 (FGFR1) or its dominant negative mutant (delta FGFR1). Cells infected with virus producing FGF ligand migrated into the somatopleure without differentiating into myotomal muscle, but differentiated into muscle fibers when they arrived in the limb bud. In contrast, cells overexpressing FGFR1 migrated into the limb muscle mass but remained as undifferentiated myoblasts. Cells infected with the delta FGFR1-producing virus failed to migrate to the somatopleure but were capable of differentiating into myotomal muscle within the somites. These results suggest that the FGFR-mediated FGF signaling (1) blocks terminal differentiation of myogenic cells within the somite and (2) sustains myoblast migration to limb buds from the somite, and that (3) down-regulation of FGFRs or FGFR signaling is involved in mechanisms triggering terminal differentiation of the limb muscle mass during avian embryogenesis.