Significant progress has been made in defining mechanisms governing myogenesis at the transcriptional levels, but the extracellular signal-transduction pathways involved in myogenesis are not as yet defined. The developing mouse tongue provides a model for the regulation of myogenesis during precise time periods in embryogenesis. The molecular cues that regulate the close-range autocrine and/or paracrine signalling processes required for the fast-twitch complex tongue musculature are not known. This study was designed to test the hypothesis that transforming growth factor-alpha (TGF alpha) controls myogenesis in embryonic mouse tongue through the induction of myogenic regulatory factors such as myoD, myf5, myogenin and MRF4/myf6/herculin. To test this hypothesis, the effects of exogenous TGF alpha on the transcription of myoD, myf5, myogenin, MRF4 and desmin were examined in tongue samples from embryonic day-10.5 mandibular explants cultured in serum-free, chemically defined medium and then processed for competitive, reverse transcription-polymerase chain reaction. TGF alpha induced myoD, myogenin and desmin expression. Treatment with 20 and 40 ng/ml TGF alpha decreased or downregulated myf5 mRNA. MRF4 was not detected in the explants. TGF alpha apparently induces the early developmental stages of myogenesis through sequential upregulation of myoD and myogenin, downregulation of myf5 and corresponding significant increases in muscle-specific gene expression such as desmin transcription.