COMBINATORIAL CONTROL OF DROSOPHILA MEF2 GENE-EXPRESSION IN CARDIAC AND SOMATIC MUSCLE-CELL LINEAGES

The Drosophila mef2 gene encodes a MADS domain transcription factor re quired for the differentiation of cardiac, somatic, and visceral muscl es during embryogenesis and the patterning of adult indirect flight mu scles assembled during metamorphosis, A prerequisite for D-MEF2 functi on in myogenesis is its precise expression in multiple cell types duri ng development. Novel enhancers for D-mef2 transcription in cardiac an d adult muscle precursor cells have been identified and their regulati on by the Tinman and Twist myogenic factors have been demonstrated. Ho wever, these results suggested the existence of additional regulators and provided limited information on the specification of progenitor ce lls for different muscle lineages. We have further characterized the h eart enhancer and show it is part of a complex regulatory region contr olling the activation and repression of D-mef2 transcription in severa l cell types. The mutation of a GATA sequence in the enhancer changes its specificity from cardial to pericardial cells, Also, the addition of flanking sequences to the heart enhancer results in expression in a new cell type, that being the founder cells of a subset of body wall muscles, As tinman function is required for D-mef2 expression in both the cardial and founder cells, these results define a shared regulator y DNA that functions in distinct lineages due to the combinatorial act ivity of Tinman and other factors that work through adjacent sequences , The analysis of D-mef2-lacZ fusion genes in mutant embryos revealed that the specification of the muscle precursor cells involved the wing less gene and the activation of a receptor tyrosine kinase signaling p athway.