Introduction
Eye of newt, and toe of frog,
Wool of bat, and tongue of dog,
Adder's fork, and blind-worm's sting,
Lizard's leg, and owlet's wing,
For a charm of powerful trouble,
Like a hell-broth boil and bubble.
(Act IV, Scene 1, Shakespeare's Macbeth)
Animals are social beings and must communicate effectively with other members of their society to signal their reproductive fitness, to find mates and to warn off predators and competitors. In most organisms, including plants, microbes and insects, much of this communication is achieved via a cocktail of released chemicals1, 2. Because specific ingredients of these complex mixtures can elicit stereotyped behavioral and developmental responses in both conspecific and heterospecific individuals2, the precise chemical composition of these complex signals must be highly regulated. The free-living soil nematode C. elegans has long been known to secrete 'dauer pheromone', a complex mixture of fatty acids that serves as a measure of the local population density3, 4. However, for the past 25 years, the influence of this pheromone has been studied using crude conditioned media—a veritable eye of newt and toe of frog potion. Black magic has now transformed to science with the publication of two papers describing specific compounds that comprise the pheromone activity, one of which appears in this issue5.
One of the main consequences of high dauer pheromone concentrations is to trigger entry of L1/L2 larval stage animals into the alternate non-aging dauer diapause state, which allows them to survive adverse conditions for long periods. The dauer pheromone has also been reported to increase longevity6, alter egg-laying rates3, and mediate changes in neuronal gene expression7, 8, perhaps to enable rapid behavioral changes in order to seek greener pastures (Fig. 1). Thus, the response to pheromone serves purposes similar to those served by bacterial quorum-sensing, in which levels of released molecules signal population density and cause population-wide changes in behavior and gene expression1. Given the critical role of dauer pheromone in the life of C. elegans, it is important to define the active chemical components, and to dissect their functional roles.
Figure 1: The structures of three known components of the C. elegans dauer pheromone, with possible aspects of behavior and development that they may affect.
Previous studies with crude pheromone preparations have suggested influences on each of these aspects, which can now be confirmed and studied rigorously with pure pheromone components.
Full size image (20 KB)An initial step toward this goal was reported by Jeong et al.9, who purified a glycoside of ascarylose from worm conditioned medium, which they dubbed daumone. However, although both natural and synthetic daumone were effective in triggering dauer formation, there were hints that daumone was not the most active component. Butcher et al.5 set out to identify these missing components. By serial fractionation of worm conditioned medium, they identified not only the previously identified daumone, but also two additional ascarosides that were more abundant in the medium extract than daumone. Each of these newly identified ascarosides was two orders of magnitude more potent than daumone in inducing dauer formation in either the natural or synthetic form. Combinations of these different ascarosides were slightly more active in inducing dauer formation than each compound alone. The authors noted that additional ascarosides were also present in the extracts at lower concentrations, which indicates that dauer pheromone may contain additional active components.
A number of interesting issues are raised by these findings. Do the individual components of dauer pheromone have distinct effects beyond triggering dauer entry? The effects of each of these ascarosides on other dauer pheromone–mediated effects have not yet been examined, leaving open the possibility that each of these components has specialized roles. This possibility is consistent with findings in other animals in which each component of an emitted chemical blend elicits a distinct response2. The precise ratio of each component in a mixture can also have a role in providing species-specific information2. Daumone was shown to induce dauer formation in the related species C. briggsae9, which shares the same ecological niche as C. elegans. However, the effects of the ascarosides identified by Butcher et al., or of mixtures of these compounds, on dauer formation in C. briggsae or other inhabitants of their ecological niche, have not yet been examined. It is also possible that the concentration of each component differs under different environmental conditions, or even at different developmental stages. In other animals, sexually mature individuals produce distinct pheromones from immature individuals; perhaps the chemical profile of pheromones produced by adult C. elegans is distinct from that of larval animals.
It has been argued that dauer pheromone is not a true pheromone—that is, a signal that provides selective advantages for both the sender and the receiver—but instead is merely a cue providing information only to the receiver10. The current study does not resolve this issue, but it is an important step toward dissecting the exact role of the dauer pheromone. The next important steps will be to dissect the functions of each individual component, investigate the metabolic pathways that result in their production, and explore the signal transduction pathways required for the responses. With specific compounds in hand, research on dauer formation has now graduated from medieval witches' brew to modern science.
