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

Bone morphogenetic protein (BMP) signaling patterns secondary body axes throughout Bilateria and in the bilaterally symmetric corals and sea anemones. Chordin-mediated "shuttling" of BMP ligands is responsible for the BMP signaling gradient formation in many bilaterians and, possibly, also in the sea anemone Nematostella, making BMP shuttling a candidate ancestral mechanism for generating bilaterality. However, Nematostella Chordin might be a local inhibitor of BMP rather than a shuttle. To choose between these options, we tested whether extracellular mobility of Chordin, a hallmark of shuttling but dispensable for local inhibition, is required for patterning in Nematostella. By generating localized Chordin sources in the Chordin morphant background, we showed that mobile Chordin is necessary and sufficient to establish a peak of BMP signaling opposite to Chordin source. These results provide evidence for BMP shuttling in a bilaterally symmetric cnidarian and suggest that BMP shuttling may have been functional in the potentially bilaterally symmetric cnidarian-bilaterian ancestor.