- Expression of four sarcomeric myosin heavy chain (MHC) genes was examined in continuously passaged human fetal (18-22 week) skeletal myoblasts and in myoblasts induced to differentiate by low mitogen medium. Although embryonic MHC mRNA predominated at all time points following induction, three additional MHC genes were expressed at lower levels. These consisted of perinatal, slow, and fast skeletal MHC genes. Temporal regulation of MHC gene expression was observed. In myoblasts and early induced cultures, embryonic and fast transcripts were detected, accompanied in later induced cultures by the accumulation of perinatal and slow MHC transcripts. In situ hybridization analysis of uninduced cells revealed that sarcomeric MHC transcripts originated from a small population of spontaneously fused multinucleated cells. Taken together, these observations demonstrate that human fetal myoblasts induced to differentiate in culture execute a developmental program that includes temporally regulated expression of four distinct sarcomeric MHC genes.