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An ancient monoaminergic signaling system coordinates contractility in a nerveless sponge
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An ancient monoaminergic signaling system coordinates contractility in a nerveless sponge

Rong Xuan Zang, Nawaphat Malaiwong, Ling Wang +13 more
February 2026
 ·
bioRxiv
 ·
DOI 
10.64898/2026.02.14.704838
94
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It ranks in the top 1% of preprints assessed in Evolutionary Biology this quarter.
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Why this is interesting

By showing that nerveless sponges synthesize monoamines through non-canonical enzymes to drive coordinated behavior, this work overturns the assumption that chemical neurotransmission requires neurons and traces its origins to pre-neuronal paracrine circuits.

Author perspective

What is the most important insight, discovery, or finding from your paper that you would like other scientists to know?
“

Rong Xuan Zang: Our paper is a bit more unconventional: using a non-model organism like sponges. The major question we're trying to answer is how, as animals first developed as multicellular organisms compared to unicellular organisms, they started to develop a system for the different cells to communicate with each other.

In a lot of the well-studied model systems (mice, fly, worm) we know the nervous system plays a key role in cell-cell communication, and they use neurotransmitters that often are metabolites of food. For example, serotonin is a metabolite derivative of amino acids. What we found is that these sponges use a more primitive version of that signaling system, where they use simple monoamines derived from amino acids. They don't use the enzyme that neurons use, but they actually use these other classes of enzymes that we discovered are functional.

This may resemble an ancestral state of how animal cells were talking to each other—using these simple monoamines as food derivatives for coordinating body behaviors. We also looked at how these sponges behave in response to these monoamines. We showed that they do some contraction that's not using the typical machinery we find in muscles, but is actually similar to chemotaxis machinery.

It seems to suggest a hypothetical scenario where, during early animal evolution, there was a division of labor and you created two different cell types: a cell type that interconverted environmental cues (food resources like amino acids) into these processed monoamines, and then those monoamines were sent as an intercellular signal within the multicellular organism. That activated specialized contractile networks of cells, a chemotaxis network that was previously autonomous in the unicellular organism, which has been incorporated with cell junction machinery to perform more coordinated and complex behaviors.

Jacob M. Musser: One of the cool things, too, is that the system of diffusing these modified metabolites is still present in us. Serotonin and dopamine are just modified a little bit further, and we still see them modulating peristalsis in our gut. We see them modulating the opening and closing of the capillary system. That's very similar to what's happening when sponges are opening and closing the feeding canals they have—they're built around a series of tubes.

So that ancient modulation system—being able to respond to your environment and regulate your feeding and fluid flow—is really the ancient system that the cells were talking about in early animals: What are we eating? What's going on in our environment? And how does our body respond to that?

”
Rong Xuan Zang
&
Jacob M. Musser

QED claims analysis

Summary

Nerveless sponges possess an ancestral monoaminergic signaling system in which secretory metabolocytes and neuroid cells synthesize tryptamine, phenethylamine, and tyramine through noncanonical decarboxylases and vesicular transporters, and these monoamines activate GPCR-coupled RhoA-Rock and Gβγ pathways in spatially segregated contractile epithelia to coordinate distinct canal behaviors, establishing that chemical transmitter systems linking secretory and contractile cell types predate neurons and were later elaborated for synaptic neuromodulation.

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Main Claim 1 –

Monoamines elicit distinct canal behaviors in sponges

Main Claim 2 –

S. lacustris synthesizes tryptamine, phenethylamine, and tyramine de novo

Supporting evidence

  • Noncanonical Pdxdc/Svop/Slc17 toolkit enables sponge monoamine signaling
  • Sponge monoamine enzymes and transporters predate canonical AADC/VMAT
  • Metabolocytes express Pdxdc1/Svop; neuroid cells express Pdxdc2/Slc17a1-8
Main Claim 3 –

Tryptamine activates GPCR–Rho signaling to remodel canal actomyosin

Supporting evidence

  • Tryptamine triggers NO-cGMP, stress, and ECM transcriptional programs
  • Candidate sponge monoamine GPCRs span classes, expressed in contractile cells
  • Spatially segregated canal contractile cells regulate distinct canal regions
Main Claim 4 –

RhoA–ROCK and Gβγ signaling drive tryptamine-induced canal remodeling

Supporting evidence

  • Tryptamine increases vinculin foci and pMYL via distinct pathways

Abstract

Chemical neurotransmission was a key animal innovation, enabling multicellular coordination of physiology and locomotion. Sponges are early-diverging animals that lack neurons and muscles, yet still coordinate contraction and relaxation of their filter-feeding water canals. Here, we show that Spongilla lacustris synthesizes the monoamines tryptamine, phenethylamine, and tyramine to elicit distinct canal behaviors. We identify previously uncharacterized decarboxylases and vesicular transporters coexpressed in secretory neuroid and metabolic cells. Using phosphoproteomics and label-free 3D imaging, we show that tryptamine activates GPCR signaling and Rho GTPases, remodeling adhesion and actomyosin networks in contractile canal epithelia to drive localized constrictions and whole-body deflations. Together, these findings define an ancestral monoaminergic system linking secretory and contractile cell types that predate neurons and was later elaborated for neuromodulation of synaptic transmission.

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