Potential for host-symbiont communication via neurotransmitters and neuromodulators in an aneural animal, the marine sponge Amphimedon queenslandica

Bilaterian DRD and TAAR-like agonists and antagonists significantly weakened the ability of the larvae to swim away from light, consistent with the sponge being able to respond to dopamine and trace amines. The impact of both dopamine agonist and antagonist on phototaxis is markedly less than that of three trace amines, phenethylamine, tyramine and tryptamine, and of a general TAAR agonist, suggesting the A. queenslandica receptors expressed in the pigment ring cells are more sensitive to trace amines than dopamine. Although it is currently unknown if the signal transduction pathways are activated by these receptors in A. queenslandica larvae, conserved genes involved in GPCR signal transduction are significantly upregulated in these pigment ring cells compared to all other larval cell types. These genes include adenylate cyclase, phospholipase C, phosphodiesterases and guanylyl cyclase (Wong et al., 2022). In addition, agonists and antagonists of GPCR and calcium intracellular signalling pathways have similar effects as the DRD and TAAR-like agonists, consistent with these affecting sponge phototaxis through receptor-mediated pathways that are similar to bilaterian GPCR pathways (Wong et al., 2022). As further support for DRD and TAAR-like agonists and antagonists affecting A. queenslandica receptors, we exposed larvae to the two trace amines with the strongest affect, phenethylamine and tyramine, and then washed and re-exposed these larvae to the light gradient in FSW. These larvae exhibited normal negative phototaxis, suggesting that the trace amines are indeed interacting with a receptor, as their dilution abrogated their agonistic effects.

There are three ancient lineages of extant animals that appeared to have diverged over 700 million years ago, before the Cryogenian (Snowball Earth): the ctenophores; sponges; and parahoxozoans (bilaterians, cnidarians and placozoans) (Ryan et al., 2010; Simion et al., 2017; Erwin, 2020; Schultz et al., 2023). Minimally, their last common ancestor had a diversity of cell types that formed an integrated and homeostatic body plan with sensory cells and complex intercellular signalling to adjust cell states and physiologies to changing developmental and environmental conditions. It seems likely that this ancestor existed in a symbiotic relationship with microbes (that is, as a holobiont) and thus also had endogenous interkingdom signalling (McFall-Ngai et al., 2013).

Recognisable nervous systems exist in ctenophores and parahoxozoans, although neural cell structure and composition differs markedly between representatives of these lineages (Burkhardt and Jékely, 2021; Moroz et al., 2021; Moroz and Romanova, 2022; Burkhardt et al., 2023). Sponges have cell types that co-express proteins comprising macromolecular complexes in ctenophore and parahoxozoan synapses, and regulatory factors that have strong proneural activity in bilaterians (Sakarya et al., 2007; Richards et al., 2008; Conaco et al., 2012; Wong et al., 2019; Musser et al., 2021). Many of these proteins are also present in choanoflagellates and other holozoan relatives, although there appear to have been innovations along the bilaterian lineage in relation to monoamine signalling (Alié and Manuel, 2010; Burkhardt, 2015; Goulty et al., 2023). Together, this suggests that at least some of the chemical signalling used in neural synapses and aneural animals existed before the divergence of ctenophore, sponge and parahoxozoan lineages.

In humans and other animals, bacteria produce metabolites that are the same as neurotransmitters and neuromodulators, and can affect the host’s nervous, endocrine and immune systems (Carabotti et al., 2014; Mazzoli and Pessione, 2016; Klimovich and Bosch, 2018; Martin et al., 2018; Bathia and Bosch, 2020; Silva et al., 2020). The ability of bacterially derived dopamine and trace amines to affect A. queenslandica larval behaviour, potentially via Rh-GPCRs and their downstream signal transducers, indicates that these known neurotransmitters and neuromodulators can be interkingdom signals even in an animal without neurons. This raises the possibility that symbiont-host communication in stem metazoans contributed to the origin of the disparate nervous systems and aneural signalling systems present in the three basal lineages. This interkingdom signalling may have emerged as an outcome of another deeply ancient system for detecting extracellular signals, the innate immune system, which discriminates self from nonself, and symbionts from pathogens and food (Bosch, 2012; Hentschel et al., 2012; McFall-Ngai et al., 2013; Klimovich and Bosch, 2018). The origin of both innate immunity and neural signalling may trace back to early stem multicellular animals that relied on associated bacteria to regulate development and cell states, as observed in some extant choanoflagellates (Alegado and King, 2014; Woznica et al., 2016; Woznica and King, 2018).

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary material.

SD and BD conceptualized this project and the methodological strategies, except for statistical methods that were conceptualized by SB. XX and AV conducted all bioinformatic analyses and experimental assays, with assistance from HY. SB conducted all statistical analyses. AV, SD, BD, XX, and SB prepared the original draft of text and figures. BD and SD finalised the drafts. All authors read and approved the final manuscript.