The unique neuronal structure and neuropeptide repertoire in the ctenophore Mnemiopsis leidyi shed light on the evolution of animal nervous systems
Posted on: 23 April 2021
Preprint posted on 31 March 2021
Article now published in Current Biology at http://dx.doi.org/10.1016/j.cub.2021.09.005
Old leidyi’s weird neurons reveal the ancient origins of the nervous system
Selected by G. Robert Aguilar
Categories: developmental biology, evolutionary biology, neuroscience, zoology
Background
Much of neuroscience is dedicated to understanding how neurons develop and give rise to complex sensations and behaviors. However, despite significant progress in these fronts, we still do not know a lot about how these fascinating cells might have evolved.
Maria Sachkova and colleagues attempt to answer this question by studying the ctenophore Mnemiopsis leidyi. Characterized, among other things, by the unique cilia they use to move, ctenophores are believed to be one of the world’s most ancient animals. How ancient? Well, that’s up for debate. While it has long been thought that neuron-less sponges are the oldest animal lineage, recent genomic studies suggest that ctenophores might be more ancient1,2. This ambiguity isn’t just evolutionary biologists nitpicking; it has profound implications for our understanding of the evolution of the nervous system. These recent findings may imply that either the nervous system was lost in sponges and placozoans, or that it evolved in ctenophores independently of other metazoans.
A more detailed study of the M. leidyi nervous system should shed light on these early stages of nervous system evolution. Considering that primordial nervous systems might have heavily relied on neuropeptide-like signaling, the authors zeroed in on the neuropeptide repertoire of M. leidyi.
Key Findings
-
Ctenophores express a diverse repertoire of neuropeptides
The authors used a machine-learning tool called NeuroPID to predict neuropeptide precursors. Instead of using sequence similarity, NeuroPID makes predictions guided by the biophysical, chemical, and statistical properties of neuropeptides and their precursors3. Their analysis revealed 129 candidates, 16 of which were found to have at least one homolog in known ctenophore transcriptomes and genomes. None had homologs in other metazoans.
To validate these putative neuropeptides, they homed in on candidates which, as previous transcriptomic profiling revealed, were expressed during the time window corresponding to neural development. Through in situ RNA hybridization (ISH) and immunohistochemistry (IHC), they showed that these candidates are concentrated in the neuro-sensory system.
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These neuropeptides affect swimming behavior
To see if the putative neuropeptides affect behavior, the authors synthesized the peptides and added them into the artificial seawater medium for the animals. Out of 9 synthesized peptides tested, four elicited a significant increase in swimming velocity. These peptides were expressed in regions of M. leidyi involved in the regulation of comb beating frequency and hunting behavior, suggesting a possible mechanism for their mode of action. It is possible that the peptides which did not produce an effect in this experiment could be involved in other behaviors or could act in concert with other neurochemicals, hypotheses which the authors did not test.
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These neuropeptides confirm the neuronal identity of some previously uncharacterized cells in the ctenophore single-cell transcriptome
A previous single-cell transcriptome of M. leidyi4 failed to identify cells which showed neuron-like expression signatures. By comparing it with their neuropeptide ISH and IHC expression data, the authors were able to assign neuronal identities to some uncharacterized cells in the single-cell transcriptome. These neurons might have been missed in the previous study because of the unique features of M. leidyi neurons. In particular, the authors show that a group of cells in the previous study called C33 corresponded to subepithelial nerve net (SNN) neurons. In addition to neuropeptides, C33 also expressed structural components indicative of neuronal identity.
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Ctenophore neurons have unique morphology
To study the ultrastructure of SNN neurons, the authors employed volume electron microscopy. Surprisingly, this analysis revealed that M. leidyi neurites show anastomoses: that is, they are fused to each other at several points through continuous membrane.
There is no other known metazoan neuron which displays this morphology. While the function of these structures is currently unknown, one hypothesis is they may accelerate or amplify neural signaling.
3D reconstruction of serial block-face scanning electron microscopy (SBF-SEM) showing the subepithelial nerve net beneath two comb rows
Overall, while these findings are far from definitively settling the debate on the evolution of the first nervous system, they pave the way for more mechanistic interrogations of M. leidyi neurobiology towards the goal of understanding how the first neurons came to be.
On a personal note
I think that “how life evolved to sense the world” is one of biology’s most consequential questions, probably second only to “how life came to be on this planet.” We are often so proud that our brains distinguish us from other animals; it is humbling to think that it should have its origins in unassuming sea creatures most of us don’t even know about.
References
- Moroz, L. L. et al. The ctenophore genome and the evolutionary origins of neural systems. Nature 510, 109-114, doi:10.1038/nature13400 (2014).
- Ryan, J. F. et al. The Genome of the Ctenophore Mnemiopsis leidyi and Its Implications for Cell Type Evolution. Science 342, 1242592, doi:10.1126/science.1242592 (2013).
- Ryan, J. F. Did the ctenophore nervous system evolve independently? Zoology 117, 225-226, doi:https://doi.org/10.1016/j.zool.2014.06.001 (2014).
- Sebé-Pedrós, A. et al. Early metazoan cell type diversity and the evolution of multicellular gene regulation. Nature Ecology & Evolution 2, 1176-1188, doi:10.1038/s41559-018-0575-6 (2018).
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