D-MEF2 IS A TARGET FOR TINMAN ACTIVATION DURING DROSOPHILA HEART DEVELOPMENT

The NK-type homeobox gene tinman and the MADS box gene D-mef2 encode t ranscription factors required for the development and differentiation of the Drosophila heart, and closely related genes regulate cardiogene sis in vertebrates. Genetic analyses indicate that tinman and D-mef2 a ct at early and late steps, respectively, in the cardiogenic lineage. However, it is unknown whether regulatory interactions exist between t hese developmental control genes, We show that D-mef2 expression in th e developing Drosophila heart requires a novel upstream enhancer conta ining two Tinman binding sites, both of which are essential for enhanc er function in cardiac muscle cells. Transcriptional activity of this cardiac enhancer is dependent on tinman function, and ectopic Tinman e xpression activates the enhancer outside the cardiac lineage, These re sults define the only known in vivo target for transcriptional activat ion by Tinman and demonstrate that D-mef2 lies directly downstream of tinman in the genetic cascade controlling heart formation in Drosophil a.