Chordin-mediated BMP shuttling patterns the secondary body axis in a cnidarian

BMP signaling patterns secondary body axes throughout Bilateria and, strikingly, in the bilaterally symmetric corals and sea anemones - members of the bilaterian sister clade Cnidaria. It has been suggested that the secondary, "directive" axis in the sea anemone Nematostella vectensis requires Chordin-mediated "shuttling" of BMP ligands, like in Drosophila or frog, however, an alternative "local inhibition" model is also possible. To choose between these two options, we generated localized Chordin sources in the Chordin morphant background and showed that in the presence of BMP ligands in Nematostella, mobile Chordin is necessary and sufficient to establish a peak of BMP signaling at the side of the embryo opposing the Chordin source. In contrast, membrane-tethered Chordin-CD2 promotes weak BMP signaling within the Chordin-CD2 source. These results provide the first mechanistic evidence for BMP shuttling in a cnidarian and suggest that BMP shuttling may have been functional in the cnidarian-bilaterian ancestor.