Arkadia enhances nodal-related signalling to induce mesendoderm

Nodal-related members of the transforming growth factor (TGF)-beta family r egulate the induction of mesoderm, endoderm, and mesendoderm, a tissue spec ific to the Spemann organizer(1-7). How these different tissues form in res ponse to the same signalling molecules is not completely understood. It has been suggested that concentration-dependent effects, mediated by extracell ular cofactors and antagonists, are responsible for the differences(1,8-10) . Here we show that the nuclear protein Arkadia specifically potentiates th e mesendoderm-inducing activity of a subset of TGF-beta family members. The combined activities of Arkadia and Xenopus nodal-related-1 are sufficient to induce mesendoderm and suppress mesoderm. Arkadia dorsalizes ventral tis sues, resulting in the induction of organizer-specific gene expression. Blo cking nodal signalling extracellularly inhibits these effects. Arkadia infl uences nodal activity when co-expressed and can function in cells adjacent to those producing the nodal signal. Our findings, together with the observ ation that Arkadia mutant mice lack a node and node-derived mesendoderm, id entify Arkadia as an essential modulator of the nodal signalling cascade th at leads to induction of Spemann's organizer.