DIVERGENT ROLES FOR NK-2 CLASS HOMEOBOX GENES IN CARDIOGENESIS IN FLIES AND MICE

Recent evidence suggests that cardiogenesis in organisms as diverse as insects and vertebrates is controlled by an ancient and evolutionaril y conserved transcriptional pathway In Drosophila, the NK-2 class home obox gene tinman (tin) is expressed in cardiac and visceral mesodermal progenitors and is essential for their specification. In vertebrates, the tin homologue Nkx2-5/Csx and related genes are expressed in early cardiac and visceral mesodermal progenitors. To test for an early car diogenic function for Nkx2-5 and to examine whether cardiogenic mechan isms are conserved, we introduced the mouse Nx2-5 gene and various mut ant and chimeric derivatives into the Drosophila germline, and tested for their ability to rescue the tin mutant phenotype, While tin itself strongly rescued both heart and visceral mesoderm, Nkx2-5 rescued onl y visceral mesoderm, Other vertebrate 'non-cardiac' NK-2 genes rescued neither. We mapped the cardiogenic domain of tin to a unique region a t its N terminus and, when transferred to Nkx2-5, this region conferre d a strong ability to rescue heart. Thus, the cardiac and visceral mes odermal functions of Nk-2 homeogenes are separable in the Drosophila a ssay. The results suggest that, while tin and Nkx2-5 show close functi onal kinship, their mode of deployment in cardiogenesis has diverged p ossibly because of differences in their interactions with accessory fa ctors. The distinct cardiogenic programs in vertebrates and flies may be built upon a common and perhaps more ancient program for specificat ion of visceral muscle.