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Thomas Lund Koch:
Molecular evolution of peptide signaling in Placozoa and Cnidaria

Date: 30-10-2020    Supervisor: Cornelis J.P. Grimmelikhuijzen & Frank Hauser



Background: Nervous systems are found almost throughout the animal kingdom, but when and how the nervous system evolved are still some of the big, unanswered questions in biology. To answer these questions it is necessary to investigate the early-branching animal phyla: Porifera, Ctenophora, Placozoa and Cnidaria, of which placozoans and cnidarians are the closest relatives of bilaterians. Neuropeptides are some of the oldest and most conserved signaling molecules of the nervous system with key roles in both bilaterian and cnidarian biology. Few years ago neuropeptides were found to be present in placozoans as well – a surprise as placozoans are believed to be animals without a nervous system. Due to the knowledge gap in neuropeptide signaling systems of Placozoa and Cnidaria the aim of this thesis was to investigate the peptidergic systems of these two phyla and to compare them. This would better enable us to understand the role of neuropeptides in the evolution of the nervous system.

Results: Using a novel search strategy I performed the first global neuropeptide annotation in all placozoan and cnidarian classes and found that their neuropeptide repertoires are much larger than previously thought. The set of cnidarian neuropeptides varies a great deal between the classes, even thought they almost all share a core set of primordial neuropeptides: GRFamides, GLWamides and XPRXamides. The three investigated placozoans, in contrast, express the same set of neuropeptides. Even though Placozoa and Cnidaria may be sister phyla there are no apparent orthology between neuropeptide families in the two phyla; and neither to any bilaterian neuropeptides. Only few antibodies have been used to localize cnidarian neuropeptides, which gives a less than optimal accuracy and resolution of their nervous system. In order to improve this we employed specific antibodies against novel Tripedalia cystophora neuropeptides and found a previously unrecognized complexity of the cubozoan nervous system. This might explain the behavioral complexity seen in this cnidarian subclass. Placozoans, on the other hand, don’t have neurons that could be stained by neuropeptides (pQFFNPamide and pQANLKSIFGamide) or neuropeptide processing enzymes (glutaminyl cyclase), which instead are expressed in different subpopulations of gland cells around the rim of the animal or scattered in the interior. Based on this finding I conclude that placozoans don’t have peptidergic neurons but endocrine cells. Staining of placozoan fiber cells however show that this cell type possess a morphology like nerve cells with processes. Additionally, I find that placozoan G protein-coupled receptors in Placozoa are more diverse than previously thought, in particular leucine rich repeat receptors.

Conclusion: Placozoans and cnidarians are situated at opposite borders of the presence and absence of a nervous system. Despite their large differences in both morphological and behavioral complexity, genetically they both possess the necessary molecular machinery for peptidergic signaling. Cnidarians employ neuropeptides primarily in nerve cells, whereas placozoan peptide signaling is based on endocrine gland cells. It is likely that neuropeptides were first employed by secretory gland-like cells and were only adapted by nerve cells at a later stage in evolution.