EXPRESSION OF THE SMOOTH-MUSCLE CELL CALPONIN GENE MARKS THE EARLY CARDIAC AND SMOOTH-MUSCLE CELL LINEAGES DURING MOUSE EMBRYOGENESIS

Although several genes are considered markers for vascular smooth musc le cell (SMC) differentiation, few have been rigorously tested for SMC specificity in mammals, particularly during development where conside rable overlap exists between different muscle gene programs. Here we d escribe the temporospatial expression pattern of the SMC calponin gene (formerly hi or basic calponin) during mouse embryogenesis and in adu lt mouse tissues and cell lines. Whereas SMC calponin mRNA expression is restricted exclusively to SMCs in adult tissues, during early embry ogenesis, SMC calponin transcripts are expressed throughout the develo ping cardiac tube as well as in differentiating SMCs. Transcription of the SMC calponin gene initiates at two closely juxtaposed sites in th e absence of a consensus TATAA or initiator element. Transient transfe ction assays in cultured SMC demonstrated that high level SMC calponin promoter activity required no more than 549 nucleotides of 5' sequenc e. In contrast to the strict cell type-specificity of SMC calponin mRN A expression, the SMC calponin promoter showed activity in several cel l lines that do not express the endogenous SMC calponin gene. These re sults demonstrate that SMC calponin responds to cardiac and smooth mus cle gene regulatory programs and suggest that the cardiac and smooth m uscle cell lineages may share a common gene regulatory program early i n embryogenesis, which diverges as the heart matures. The finding that the isolated SMC calponin promoter is active in a wider range of cell s than the endogenous SMC calponin gene also suggests that long-range repression or higher order regulatory mechanism(s) are involved in cel l-specific regulation of SMC calponin expression.