Analysis of SMAD1/5 target genes in a sea anemone reveals ZSWIM4-6 as a novel BMP signaling modulator

BMP signaling has a conserved function in patterning the dorsal-ventral body axis in Bilateria and the directive axis in anthozoan cnidarians. So far, cnidarian studies have focused on the role of different BMP signaling network components in regulating pSMAD1/5 gradient formation. Much less is known about the target genes downstream of BMP signaling. To address this, we generated a genome-wide list of direct pSMAD1/5 target genes in the anthozoan Nematostella vectensis, several of which were conserved in Drosophila and Xenopus. Our ChIP-Seq analysis revealed that many of the regulatory molecules with documented bilaterally symmetric expression in Nematostella are directly controlled by BMP signaling. Among the so far uncharacterized BMP-dependent transcription factors and signaling molecules we identified several, whose bilaterally symmetric expression may be indicative of their involvement in secondary axis patterning. One of these molecules, zswim4-6, encodes a novel nuclear modulator of the pSMAD1/5 gradient potentially promoting BMP-dependent gene repression. Strikingly, overexpression of the zebrafish homologue zswim5 suggests that its effect on the pSMAD1/5 gradient is conserved between anthozoan Cnidaria and Bilateria.