FGF5 stimulates expansion of connective tissue fibroblasts and inhibits skeletal muscle development in the limb

FGF5 is expressed in the mesenchyme and skeletal muscle of developing and a dult mouse limbs. However, the function of FGF5 during development of the l imb and limb musculature is unknown, To elucidate the inherent participatio n of FGF5 during limb organogenesis, a retroviral delivery system (RCAS) wa s used to overexpress human FGF5 throughout developing hind limb of chicken embryos. Misexpression of the soluble growth factor severely inhibited the formation of mature myocytes. Limbs infected with RCAS-FGF5 contained smal ler presumptive muscle masses as evidenced by a decrease in MyoD and myosin heavy chain expressing cells. In contrast, ectopic expression of FGF5 sign ificantly stimulated proliferation and expansion of the tenascin-expressing , connective-tissue fibroblast lineage throughout the developing limb. Hist ological analysis demonstrated that the increase in tenascin immunostaining surrounding the femur, ileum, and pubis in the FGF5 infected limbs corresp onded to the fibroblasts forming the stacked-cell perichondrium, Furthermor e, pulse labeling experiments with the thymidine analog, BrdU, revealed tha t the increased size of the perichondrium was attributable to enhanced cell proliferation. These results support a model whereby FGF5 acts as a mitoge n to stimulate the proliferation of mesenchymal fibroblasts that contribute to the formation of connective tissues such as the perichondrium, and inhi bits the development of differentiated skeletal muscle. These results also contend that FGF5 is a candidate mediator of the exclusive spatial patterni ng of the hind limb connective tissue and skeletal muscle. (C) 2000 Wiley-L iss, Inc.