Expression of a Murine Homeobox Gene Precedes the Induction of C-fos During Mesodermal Differentiation of P19 Teratocarcinoma Cells

The controlled expression of regulatory genes is the basis of normal mouse embryo development. Recent studies in our laboratory have revealed temporally and spatially restricted expression of homeobox-containing genes and the cellular protooncogene c-fos in developing mouse embryos. In order to gain insight into cellular control mechanisms responsible for differential expression of these potential regulatory genes during developmental processes, we set out to analyze their expression in teratocarcinoma cells as an in vitro model system for cellular differentiation. We demonstrated that the homeobox-containing gene Hox 1.3 and the c-fos protooncogene are expressed in P19 teratocarcinoma cells prior to their terminal myogenic differentiation, which is indicated by the expression of muscle-specific myosin. Using a combination of the transcriptional run-on assay and Northern analysis, we defined some of the cellular control mechanisms that are responsible for the changes in transcription pattern during P19 differentiation. The development-dependent activation of c-fos and muscle-specific myosin mRNA was found to result from an increased transcription rate. In contrast, the primary induction of Hox 1.1 (m6)-specific mRNA was controlled on the posttranscriptional level by changes in the half-life of the transcript. In addition, in situ hybridization studies revealed a characteristic spatially restricted expression of Hox 1.1 RNA in P19 aggregates, which may point to an important role of cell-cell interactions for Hox 1.1 expression in the mesodermal muscle differentiation pathway.