Expression cloning of Xenopus Os4, an evolutionarily conserved gene, whichinduces mesoderm and dorsal axis

Multiple factors, including members of the FGF, TGF beta, and Wnt family of proteins, are important mediators in the regulation of dorsal-ventral patt ern formation during vertebrate development. By using an expression cloning approach to identify novel factors that could regulate dorsal-ventral patt erning in the Xenopus embryo, we isolated the Xenopus homologue of the huma n Os4 gene by virtue of its ability to induce a secondary dorsal axis. Whil e Os4 homologues have been identified in a variety of species, and human Os 4 is overexpressed in human tumors, the biological function of Os4 is unkno wn. To explore the mechanism by which Xenopus Os4 (XOs4) induces a secondar y dorsal axis, we used Xenopus explant and whole-embryo assays. The seconda ry axis induced by XOs4 is distinct from that induced by activation of Wnt or FGF pathways but similar to that induced by inhibition of BMP signaling or activation of an Activin pathway. However, XOs4 did not inhibit BMP sign aling in dissociated animal cap explants, indicating that XOs4 does not inh ibit BMP signaling. Similar to activation of an Activin-like pathway, expre ssion of XOs4 induces molecular markers for mesoderm in animal cap explants , although expression of gastrula-stage mesodermal markers was very weak an d substantially delayed. Yet, XOs4 does not require activity of the Activin signal-transduction pathway for mesoderm induction as dominant-negative co mponents of the Activin/Nodal/Vg1 pathway did not prevent XOs4-mediated ind uction of mesodermal derivatives. Finally, like Activin/Nodal/Vg1 pathways, XOs4 requires FGF signaling for expression of mesoderm markers. Results pr esented in this study demonstrate that XOs4 can induce mesoderm and dorsali ze ventral mesoderm resulting in ectopic dorsal axis formation, suggesting a role for this large evolutionarily conserved gene family in early develop ment. (C) 2001 Academic Press.