LWamides from Cnidaria constitute a novel family of neuropeptides with morphogenetic activity

Metamorphosin A (MMA) isolated from the anthozoan Anthopleura elegantissima has recently been shown to interfere with developmental control in the colonial hydroid Hydractinia echinata. In order to identify the functional homologue in this species we have cloned cDNAs of the precursor protein from Hydractinia and, for comparison, precursor sequences from two further anthozoans. The deduced preproproteins contain multiple copies of propeptides to be processed into a great variety of novel neuropeptides most of which are N-terminally different from MMA. Original MMA is only contained in the anthozoan precursors. Most of the novel neuropeptides will have the carboxyl terminus LWamide. Therefore, we term this novel neuropeptide family the LWamides. Peptides synthesized according to the precursor sequence of H. echinata and added to planulae trigger metamorphosis. In contrast, none of 11 other known biologically active peptides including carboxamidated neuropeptides were effective. Expression analysis by in situ hybridization and by antibodies against the H. echinata peptide reveals the presence of the gene product in planulae at the proper time and at the due spatial location expected for a natural role in metamorphosis. LWamide transcripts are also observed in nerve cells of primary and adult polyps, suggesting LWamides to be a multifunctional family of neuropeptides.