The primary role of pheromones is to communicate salient social information about the sender – sex, age, status, health, etc. In C. elegans, both males and hermaphrodites (which could be thought of as being essentially female) secrete blends of social signals that consist of different molecules, chief among them ascarosides (made of a sugar and a fatty acid; two examples are shown in the figure above). Whereas the male and hermaphrodite blends are similar, they differ substantially in the relative amounts of two ascarosides – males secrete more ascr#10 than ascr#3, the opposite being true in hermaphrodites. Is this meaningful?

Aprison EZ, Ruvinsky I (2017) Counteracting ascarosides act through distinct neurons to determine the sexual identity of C. elegans pheromones. Curr. Biol. 27: 2589–2599.

Key results

1. ascr#3 counteracts the effect of ascr#10.
2. Blends of ascr#10 and ascr#3 are perceived by recipient hermaphrodites as “male” if the concentration of ascr#10 is higher than that of ascr#3, and as “hermaphrodite” if otherwise.
3. Distinct sets of sensory neurons are required in recipient hermaphrodites to respond to the signals conveyed by ascr#10 and ascr#3.

Other notable findings

1. Response to ascr#10 depends on its absolute concentration – none is seen in either the low or high range, whereas strongest responses are seen at intermediate concentrations corresponding to amounts produced by small groups of animals. This reinforces a well-established idea that pheromone responses should be studied at physiologically reasonable concentrations.
2. The function of a TGF-beta-like ligand DAF-7 is required for hermaphrodite response to ascr#10.
3. In several divergent signaling systems, when a ratio of concentrations of two components has to be assessed (as is the case for ascr#10 and ascr#3), the two signals are processed separately by dedicated circuits.

Major remaining questions

1. How are male and hermaphrodite pheromones found in nature? Based on their chemical properties, ascarosides are expected to diffuse relatively readily, thus blending and nullifying the identity of individual messages. Our experiments clearly show that this does not happen. Are pheromones released in “packets”? How do they stay together?
2. What are the specific roles of all sensory neurons implicated by our study in the hermaphrodites’ response to male pheromone?
3. What are the interneurons that presumably (!) ultimately compute the ratio of ascr#10 and ascr#3 concentrations?
4. How is the signal propagated to target tissues where effects take place?
5. Is it due to chance or necessity that different neurons are involved in response to ascr#10 and ascr#3? Giving the “necessity hypothesis” additional credence, the channels deployed by the two separate neuronal circuits are different too. This is consistent with the idea that these different mechanisms reflect a “design constraint” required for optimal detection of different signals and the eventual comparison of their relative strengths.