Components of Bone Morphogenetic Protein (BMP) signaling are highly conserved in the early diverging phylum Cnidaria, the sister clade of Bilateria. Thus far, cnidarian BMP signaling has mostly been studied in Anthozoa (sea anemones and corals), where a gradient of BMP signaling patterns their secondary, “directive” body axis, similar to dorsal-ventral axis patterning in Bilateria. In contrast, all cnidarians within Medusozoa (jellyfish) lack the directive axis, yet the entire intracellular BMP signaling machinery remains present, both in Anthozoa and Medusozoa, suggesting that there are yet unknown functions of BMP signals that are unrelated to axial patterning but indispensable for the survival of these animals.

To unravel the roles of cnidarian BMP signaling unrelated to axis patterning, we generated a morphological atlas of the BMP signaling activity in the adult polyp of the sea anemone Nematostella using an antibody against its effector, pSMAD1/5. BMP signaling was most prominent in the neuro-muscular regions of the so-called mesenteries – the folds of the gut epithelium. Combining the pharmacological attenuation of BMP activity with tissue-specific RNA-Seq, we showed that BMP signaling mostly controls developmental regulators (transcription factors, signaling molecules etc.), including many neuronal genes. Utilizing transgenic reporter lines, we discovered that BMP signaling partially overlaps with neuronal populations of the mesentery, including soxB2(+) progenitors expressing and their differentiated elav(+)/nanos1(+) progenies. Strikingly, another neuronal population expressing prdm14d never displayed active BMP signaling, suggesting BMP signaling marks only specific neuronal subpopulations. Similarly, we detected BMP signaling in parts of the nervous system of two Medusozoa representatives, the moon jellyfish Aurelia and box jellyfish Tripedalia.

Our findings provide new insights into pro-neural roles of BMP signaling in Anthozoa and Medusozoa. Moreover, the comparison to data from Bilateria indicates that pro-neural functions of BMP signaling might represent an ancient trait present already before the cnidarian-bilaterian split.