The three-banded panther worm is rewriting the story of brain evolution

Sometime in the nervous system’s deep evolutionary past, simple nerve nets, in which signals flow in all directions, gave way to complex brains parceled into regions that carry out specific functions. The unique structure of the three-banded panther worm (Hofstenia miamia) brain, however, upends any assumptions about how this transition occurred. 

The grain-of-rice-sized marine worm has three light stripes across its back and is a voracious predator of tiny invertebrates—hence its common name. Its nervous system is more condensed than a nerve net, with a closely packed concentration of nerve cells in the head. But unlike the brains of other bilaterally symmetrical organisms, such as roundworms, insects, mice and humans, it lacks specialized regions. Hofstenia’s lineage diverged from that of these other groups about 550 million years ago, near the very base of the bilaterian family tree.

The animal is also capable of regenerating its entire body from a fragment of itself, a phenomenon that Mansi Srivastava, professor of organismic and evolutionary biology at Harvard University, has studied for more than a decade. Now, Vikram Chandra, a postdoctoral researcher in Srivastava’s lab, has adapted the slice-and-dice methodology typical of those studies to investigate the worm’s nervous system. The researchers shared some of their first results from this project in a preprint posted on bioRxiv earlier this year.

Srivastava and Chandra spoke with The Transmitter about why three-banded panther worms are “great lab rats,” what the animals manage to do with half their brain missing, and what the researchers plan to do next.

This interview has been edited for length and clarity.

The Transmitter: How did you begin working with Hofstenia?

Mansi Srivastava: When I started my postdoc research years ago, I was really driven to study the evolution of regeneration. Planarian worms had become the established, go-to system for this research. But to me, insights that are about one organism are nowhere near as satisfying as evolutionary insights. So I tried working on lots of different species that gave me evolutionary distance from planarians; and acoels, a class of flatworm-like invertebrates, were always really interesting. But at that time, there was not a perfect acoel model system established in the lab. And so I actually went out and collected the species from the field. 

There’s this guy, Ulf Jondelius at the Swedish Museum of Natural History, who’s an expert on acoels. And we asked him, if you were to pick any acoel and try to grow it in the lab, which one would it be? And he pointed us to this one. So we went to Bermuda, based on a paper they had published years ago, which listed exactly the latitude and longitude where [three-banded panther worms] were last collected, and we were able to collect them. And then after that, I got super lucky. There are so many points at which new model systems will fail. But we were able to figure out ways of culturing them and got lots of tools and techniques working in them.

TT: How do you care for Hofstenia in the lab?

MS: Oh, they’re really easy. They’re great lab rats. We keep them in artificial seawater in plastic boxes, and they swim around happily. You can stick them inside a drawer. As long as there’s not too much evaporation, they’re fine; you don’t need any specific conditions. What’s nice for us is that they reproduce sexually, and they’re constantly making babies. They will lay their eggs on the sides of the boxes, so you can just go in with a little pipette and harvest the eggs. More recently, we’ve also been able to purchase an automated care system in which the water is constantly circulating, and we can keep the worms in much larger numbers. But you don’t need that. For the first nine years of my lab, we didn’t have any fancy equipment at all.

TT: How does the unique organization of Hofstenia’s nervous system relate to its behaviors?

Vikram Chandra: If you lesion a specific part of a vertebrate or an insect brain, you get a very predictable, specific defect. That’s a basic feature of brains we’ve studied so far. Hofstenia does not have that. Instead, there is a brain, which is this very dense agglomeration of neurons in the head, but within it, there’s no anatomical or functional or molecular regionalization that we can find. We can amputate arbitrary large fractions of this brain, and the animal is fine, as far as we can tell. It’s able to successfully hunt shrimp even when it’s missing half of its head, or sometimes 80 percent.

TT: What does this tell us about the evolution of brains?

MS: Many people have thought about how you go from having nerve nets to animals with brains. But there have been more proposals of the idea that you regionalize and then centralize. And our work on Hofstenia suggests the possibility that you could have the opposite, where you centralize first and regionalize later.

VC: What we’re proposing is that, given Hofstenia’s phylogenetic position and its brain architecture, this is at least a plausible intermediate state. If you took an ancient nerve net and condensed it into the head, but you didn’t yet put specific cell types in specific locations within that head, that would look sort of like the Hofstenia brain, and maybe that’s what the first brains could have looked like.  

It also suggests that you don’t really need many of the features we take for granted in typical bilaterian brains, such as regionalization, to get complex behavior. The worm is able to do pretty complicated reproductive behavior. It can hunt shrimp in ways that are quite sophisticated and quite fast-paced.

TT: What are each of you planning to do next?

MS: We’re getting more and more embroiled in embryology. I started my lab with an interest in regeneration, which in some ways is a feature of adult organisms. But our work on Hofstenia embryos has revealed just an incredible level of plasticity of the cells and a robustness throughout development. And so we’re delving deeper into questions about how plasticity in embryos and regeneration in adults relate to each other. 

VC: Next March, I’m starting a lab at the Francis Crick Institute in London. The plan is to use Hofstenia and perhaps some other acoels to understand: How is this new kind of brain organized? What is the wiring architecture of this brain? How does it compute? How does it control behavior? I’d like to find the most interesting, complicated thing a worm can do. And I’d then like to go and ask, what is a neural mechanism for that?