CONVERSION OF DERMAL FIBROBLASTS TO A MYOGENIC LINEAGE IS INDUCED BY A SOLUBLE FACTOR DERIVED FROM MYOBLASTS

The limb and axial skeletal muscles of mammals originate from semitic dermomyotome, which during early development separates to form two dis crete structures, the dermatome and the myotome. The latter cell mass gives rise to the muscle-forming lineage while cells of the dermatome will form the skin dermal fibroblast population of the dorsal regions of the body. It has been generally accepted for some time that myotome -derived myoblasts were the sole source of muscle fibre nuclei, but ev idence has recently been presented from several laboratories that fibr oblasts can fuse with myoblasts to contribute active nuclei to the res ulting myotubes. We report here an investigation into the myogenic cap acity of fibroblasts. Confluent monocultures of mouse dermal fibroblas ts, muscle fibroblasts, and C2C12 myoblasts each retain their individu al phenotype when maintained for periods up to 7 days in culture. We a lso grew isolated colonies of fibroblasts and myoblasts in an arrangem ent which allowed free exchange of tissue culture medium between the 2 cell types. We found evidence of the conversion of dermal fibroblasts to a myogenic lineage as measured by the appearance of MyoD-positive cells expressing the muscle-specific intermediate filament desmin. In addition, dermal fibroblast cultures contained multinucleate syncytia positive for MyoD and containing sarcomeric myosin heavy chain. In con trast, muscle-derived fibroblasts showed no evidence of myogenic conve rsion when maintained in identical culture conditions. We prepared con ditioned medium from confluent cultures of C2C12 myoblasts and added t his material to confluent monocultures of either dermal or muscle fibr oblasts. While muscle fibroblasts showed no phenotypic alterations, cu ltures of dermal fibroblasts responded to myoblast conditioned medium by converting to a myogenic lineage as judged by expression of MyoD an d desmin. We conclude that a proportion of dermal fibroblasts retain a myogenic capacity into stages well beyond their early association wit h myoblasts in the dermomyotome. (C) 1996 Wiley-Liss, Inc.