Male pheromones accelerate the development of hermaphrodite larvae in Caenorhabditis elegans, but the importance of this phenomenon is not well understood. A new paper in Development shows that pheromone exposure during larval stage 3 helps coordinate behaviour and development by modulating the timing of the transition to larval stage 4. To learn more about the story behind the paper, we caught up with first author Denis Faerberg who carried out the work in the lab of the corresponding author Ilya Ruvinsky at Northwestern University, USA.

Ilya Ruvinsky (left) and Denis Faerberg (right)

Ilya, what questions are your lab trying to answer?

IR: We are trying to understand the mechanisms by which social signals, primarily pheromones, affect development and physiology. One animal is trying to manipulate another. How? Why? These are terrifically interesting questions! That some of these molecules could exert their effects at picomolar concentrations implies that neuronal signalling must be involved. This makes the problem even broader – how does the nervous system regulate development? To date, we made most progress identifying neuronal circuits responsible for the effects of one type of pheromone, ascr#10, on the germline. The effects on accelerated development described in this paper are due to the activity of at least two classes of pheromones that are different from each other and from ascr#10. We expect that comparing the neuronal signalling that mediates different developmental effects of different classes of pheromones will reveal general features of neuronal circuits that regulate development.

Denis, how did you come to work in the lab and what drives your research today?

DF: I was graduating and applying for jobs when Ilya invited me to join his lab as a research technician. Ilya and Erin Aprison, our co-author on this paper, trained me to work with C. elegans nematodes, to plan and execute proper research, and even to make publication-level figures – all of which helped me enormously. More than that, delving into the literature and thinking about developmental trajectories during this project made me fall in love with development in general. Curiosity of how plasticity and optimal strategies are organized across growth, behaviour and development has been driving my research since.

Tell us about the background of the field that inspired your work

IR: In the broadest sense, our study belongs in the field of eco-devo. In nature, developmental processes function under variable environmental conditions. We must know how this happens to truly understand development. Developmental plasticity represents a particularly interesting subset of environmentally dependent developmental phenomena – in one environment, one set of developmental events occurs; in another, an alternative set. There is a rich tradition of studying developmental plasticity in C. elegans using dauer as a model. Hundreds of great papers have been written and several important pathways have been extensively studied during this effort. In a sense, we are building on that great foundation.

In nature, developmental processes function under variable environmental conditions. We must know how this happens to truly understand development.

More specifically, there were two streams of discoveries that motivated the present study. One consisted of several papers from our lab (by Erin Aprison, our co-author on this paper) and from Frank Schroeder's lab at Cornell, USA (who discovered dozens of C. elegans pheromones) that demonstrated that specific components of the complex pheromone bouquet excreted by C. elegans males hastened maturation of hermaphrodite larvae. The other was the study led by Shay Stern (now at Technion, Israel) when he was a postdoc with Cori Bargmann at Rockefeller, USA. Tracking locomotion of individual worms throughout larval development, they found that there was considerably more exploratory movement in early compared with later parts of larval stages. This result prompted us to think about connections between larval behaviour and development. Several other studies, including those on lethargus periods between larval stages, also helped to shape our thinking.

Can you give us the key results of the paper in a paragraph?

IR & DF: Male pheromones coordinately accelerate growth and development of hermaphrodite larvae. This acceleration becomes evident around the transition between L3 and L4 larval stages. Observing larvae through this transition reveals that male pheromones lengthen the L3 stage, allowing more time to feed and grow. Better feeding in L3 appears to accelerate development in L4. There is a crucial window in the second half of L3 when larvae are receptive to the male signal. Sensing a cue in the second half of a stage and responding at the onset of the next stage is not unique to the response to the male pheromones that we described. Several other plastic developmental decisions are made in the latter part of one life stage but are implemented in the stage that follows. We discuss distinct behavioural patterns in early versus late parts of life stages – there is more global exploration early on, but greater focus on consumption of resources toward the end of the stage. Distinct behavioural epochs within life stages balance the effort needed to discover and exploit resources. We argue that these patterns reflect mechanisms that ensure flexible matching of developmental progression to specific environmental conditions. Although our study was focused on C. elegans, we propose that similar patterns should be evident in all species with larval development, and possibly beyond.

Although our study was focused on C. elegans, we propose that similar patterns should be evident in all species with larval development, and possibly beyond

When doing the research, did you have any particular result or eureka moment that has stuck with you?

DF: Yes! Seeing the difference in the duration of lethargus between L3 and L4 stages was at first confusing but later the eureka moment. The lengthening of L3 in larvae that accelerate development on male pheromones contradicted our expectation. But, having thought a bit about it, we realized that more time in L3 results in more feeding and therefore better provision for growth and faster development.

Developmental plasticity of the C. elegans life cycle. The choice of whether to follow the blue or the red alternative path of larval development, which differ in the L4 stage, is made by hermaphrodite larvae depending on the presence or absence of male pheromones.

Developmental plasticity of the C. elegans life cycle. The choice of whether to follow the blue or the red alternative path of larval development, which differ in the L4 stage, is made by hermaphrodite larvae depending on the presence or absence of male pheromones.

And what about the flipside: any moments of frustration or despair?

DF: The most frustrating part of this study was due to the extent of interindividual variability in developmental rates. By mid-larval development, some individuals are several hours ahead of others even though they started at essentially the same time. This makes it difficult to obtain precise estimates of timing of events. Although, on the other hand, this variability is what we want to study in the first place.

Why did you choose to submit this paper to Development?

IR: I felt that it was important to share our study with the community of developmental biologists because it contains notions of behaviour and the environment. What better platform than Development, which has long been the flagship journal in the field. I also like the fact that Development does not charge astronomical publication fees, as seems to be the unfortunate norm these days.

What is next for you after this paper?

DF: I'm pursuing a PhD at Princeton (NJ, USA) trying to understand general principles of organization of development. I study alternative trajectories of larval development in fruit flies and the dynamics of cell fate decisions in early mouse embryos.

Where will this story take your lab next?

IR: Circuits! We are working to identify specific neurons that systemically accelerate development in response to male pheromones, and to discover how they do it. The compact nervous system of C. elegans and the generous community of worm biologists makes this goal plausible.

Finally, let's move outside the lab – what do you like to do in your spare time?

DF: I enjoy playing boardgames and table-top role-playing games. There is a wonderful community of players at Princeton with a penchant for particularly complex games. Can't get away from thinking about strategies even on the days off!

IR: What spare time? I have little kids. That said, running along the lakefront in Chicago can be restorative, and I do enjoy reading.

Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.

E-mail: [email protected]

Faerberg
,
D. F.
,
Aprison
,
E. Z.
and
Ruvinsky
,
I.
(
2024
).
Accelerated hermaphrodite maturation on male pheromones suggests a general principle of coordination between larval behavior and development
.
Development
151
,
dev202961
.