Vertebrate tinman homologues and cardiac differentiation

In Drosophila, the homeobox gene tinman is required for specification of dorsal vessel and a number of mesodermal subtypes. Six tinman homologues have now been found in diverse vertebrate species: Nkx2-3, 2-5, 2-6, 2-7, 2-8 and 2-9. Of these, Nkx2-5 appears to be the mostly highly conserved among species, in terms of both primary protein sequence and mRNA expression pattern. Of the others, some have been found as yet only in a single species. Although expression patterns of vertebrate tinman homologues indicate that they may play a role in the specification of several mesodermal or endodermal tissues, to date most attention have been focussed on their role in cardiac development. Results of these studies indicate that, as for Drosophila tinman, vertebrate tinman homologues may be required for heart formation, but may not be sufficient. Studies in Drosophila are defining other pathways which are required in concert with tinman for dorsal vessel formation. Circumstantial evidence suggests that similar pathways may be operative in vertebrate heart formation. This review summarizes recent advances in our understanding of vertebrate tinman homologues and interacting genetic pathways.