tinman-related genes expressed during heart development in Xenopus.

The tinman homeobox gene of Drosophila is absolutely required for development of the insect heart. This observation prompted the isolation of tinman-related genes from vertebrates, in the hope that the developmental function of the gene would be conserved between evolutionarily distinct species. The first vertebrate tinman gene, Nkx2-5, was isolated from mouse and subsequently, orthologues of Nkx2-5 have been isolated from a number of different species. In all cases, a conserved pattern of Nkx2-5 expression is observed in the developing heart, commencing prior to differentiation. Genetic ablation of Nkx2-5 in the mouse results in embryonic lethality due to heart defects, but most myocardial genes are expressed normally and a beating heart tube forms. This observation raises the possibility that additional genes related to Nkx2-5 are partially rescuing Nkx2-5 function in the null mouse. Recently, additional members of the tinman-related gene family have been discovered and characterized in a number of different species. Somewhat surprisingly, orthologous genes in different organisms can be rather divergent in sequence and may show completely different expression patterns. In at least some organisms, expression of the tinman-related genes is not observed in the heart. Due to the increasing number of family members and the somewhat divergent expression patterns, the precise role of the tinman-related genes in cardiac development remains an open question. In a search for additional tinman-related genes in the frog, Xenopus laevis, we have identified Nkx2-9, a novel member of the tinman-related gene family. Preliminary characterization reveals that Nkx2-9 is expressed in the cardiogenic region of the embryo prior to differentiation, but transcript levels decrease rapidly, in the heart, at about the time that differentiation commences.