NeuroSystematics and Periodic System of Neurons: Model vs Reference Species at Single-Cell Resolution

Abstract

There is more than one way to develop neuronal complexity, and animals frequently use different molecular toolkits to achieve similar functional outcomes (=convergent evolution). Neurons are different not only because they have different functions, but also because neurons and circuits have different genealogies, and perhaps independent origins at the broadest scale from ctenophores and cnidarians to cephalopods and primates. By combining modern phylogenomics, single-neuron sequencing (scRNA-seq), machine learning, single-cell proteomics, and metabolomic across Metazoa, it is possible to reconstruct the evolutionary histories of neurons tracing them to ancestral secretory cells. Comparative data suggest that neurons, and perhaps synapses, evolved at least 2-3 times (in ctenophore, cnidarian and bilateral lineages) during ∼600 million years of animal evolution. There were also several independent events of the nervous system centralization either from a common bilateral/cnidarian ancestor without the bona fide neurons or from the urbilaterian with diffuse, nerve-net type nervous system. From the evolutionary standpoint, (i) a neuron should be viewed as a functional rather than a genetic character, and (ii) any given neural system might be chimeric and composed of different cell lineages with distinct origins and evolutionary histories. The identification of distant neural homologies or examples of convergent evolution among 34 phyla will not only allow the reconstruction of neural systems' evolution but together with single-cell "omic" approaches the proposed synthesis would lead to the "Periodic System of Neurons" with predictive power for neuronal phenotypes and plasticity. Such a phylogenetic classification framework of Neuronal Systematics (NeuroSystematics) might be a conceptual analog of the Periodic System of Chemical Elements. scRNA-seq profiling of all neurons in an entire brain or Brain-seq is now fully achievable in many nontraditional reference species across the entire animal kingdom. Arguably, marine animals are the most suitable for the proposed tasks because the world oceans represent the greatest taxonomic and body-plan diversity.

Atlas of the Neuromuscular System in the TrachymedusaAglantha digitale: Insights from the advanced hydrozoan

“…We also did not detect RFa-IR motor neurons further confirming a possibility that at least two structurally and molecularly distinct neural subsystems are present in Aglantha as in other jellyfishes (Satterlie, 2011;Eichinger and Satterlie, 2014;Satterlie and Eichinger, 2014). It would be safe to say that more novel neuronal elements and circuits would be revealed in Aglantha with additional cell-specific molecular markers as new signal molecules and transmitters would be identified using tools of single-cell genomics (Moroz, 2018).…”

Neuromuscular organization of the Ctenophore Pleurobrachia bachei

“…Recent advances of comparative single‐cell genomic point to insufficient knowledge about the cellular diversity in basal metazoans in general, and ctenophores in particular. In fact, recent single‐cell RNA‐seq profiling of two ctenophores (Moroz, ; Sebe‐Pedros et al, ) indicated that many cells could not be reliably recognized using conventional approaches. The absence of cell‐specific molecular markers for ctenophore neurons and muscles is a noticeable obstacle in the field.…”

“…In summary, both ciliated cells and muscles have greater overall morphological diversity than neurons. However, we suspect that there is a hidden molecular diversity among all cell types and mostly in ctenophore neurons, which can be revealed in the ongoing and future systematic comparisons of cell‐specific genomic, proteomic, and metabolomic studies (Moroz, ). The presented atlas of the neuro‐muscular organization in Pleurobrachia would be one of many reference platforms to understand the complex life of comb jellies better.…”

Lineage-specific diversification in the usage of D-glutamate and D-aspartate in early-branching metazoans

“…4B. Regardless of the proposed phylogenies, these four groups represent crucial taxon sampling to understand the origin and evolution of animal traits, the nervous system, and neurotransmitters in particular [45].…”