SOX7 and SOX18 are essential for cardiogenesis in Xenopus.

Early in vertebrate development, endodermal signals act on mesoderm to induce cardiogenesis. The F-type SOXs SOX7 and SOX18beta are expressed in the cardiogenic region of the early Xenopus embryo. Injection of RNAs encoding SOX7 or SOX18beta, but not the related F-type SOX, SOX17, leads to the nodal-dependent expression of markers of cardiogenesis in animal cap explants. Injection of morpholinos directed against either SOX7 or SOX18mRNAs lead to a partial inhibition of cardiogenesis in vivo, while co-injection of SOX7 and SOX18 morpholinos strongly inhibited cardiogenesis. SOX7 RNA rescued the effects of the SOX18 morpholino and visa versa, indicating that the proteins have redundant functions. In animal cap explants, it appears that SOX7 and SOX18 act indirectly through Xnr2 to induce mesodermal (Eomesodermin, Snail, Wnt11), organizer (Cerberus) and endodermal (endodermin, Hex) tissues, which then interact to initiate cardiogenesis. Versions of SOX7 and SOX18 with their C-terminal, beta-catenin interaction domains replaced by a transcriptional activator domain failed to antagonize beta-catenin activation of Siamois, but still induced cardiogenesis. These observations identify SOX7 and SOX18 as important, and previously unsuspected, regulators of cardiogenesis in Xenopus.