Chemical structure and biological activity of the Caenorhabditis elegans dauer-inducing pheromone

Abstract

Pheromones are cell type-specific signals used for communication between individuals of the same species. When faced with overcrowding or starvation, Caenorhabditis elegans secrete the pheromone daumone, which facilitates communication between individuals for adaptation to adverse environmental stimuli. Daumone signals C. elegans to enter the dauer stage, an enduring and non-ageing stage of the nematode life cycle with distinctive adaptive features and extended life. Because daumone is a key regulator of chemosensory processes in development and ageing, the chemical identification of daumone is important for elucidating features of the daumone-mediated signalling pathway. Here we report the isolation of natural daumone from C. elegans by large-scale purification, as well as the total chemical synthesis of daumone. We present the stereospecific chemical structure of purified daumone, a fatty acid derivative. We demonstrate that both natural and chemically synthesized daumones equally induce dauer larva formation in C. elegans (N2 strain) and certain dauer mutants, and also result in competition between food and daumone. These results should help to elucidate the daumone-mediated signalling pathway, which might in turn influence ageing and obesity research and the development of antinematodal drugs.

Metabolite Induction of Caenorhabditis elegans Dauer Larvae Arises via Transport in the Pharynx

“…When this screen was used, worms entered dauer development ( Figure 1, panel a) when treated with 1 at an ED 50 value of 50 ± 10 μM (Figure 1, panels b and c). This value was considerably lower than the 386 μM (see ref 11) reported using agar analyses (16). The blue fluorescent analog 4 was slightly more active and the green fluorescent analog 5 less active than 1 with ED 50 values of 20 ± 5 μM and 200 ± 25 μM, respectively.…”

Generation and modulation of chemosensory behaviors in C. elegans

“…However, chemical signals sensed during the first larval stage are essential in directing the choice of the appropriate developmental program. C. elegans constitutively secretes a pheromone that serves as a measure of population density [8][9][10]. L1 larvae assess levels of this pheromone, as well as levels of food in their environment to make a critical developmental decision.…”

“…Worms are attracted to, or avoid, different bacteria [68,105,106], and it is not yet known whether these behaviors are mediated primarily via a single bacterially produced chemical, or whether a set of chemicals must be recognized as an ensemble to provide a chemical signature for a specific bacterial strain. Similarly, although a major regulator of worm behavior and development is levels of the constitutively produced dauer pheromone [8][9][10][107][108][109], the neurons that respond to pheromone are also not yet defined. Presumably, males and hermaphrodites also produce signals to attract or repel each other, but these cues and the relevant sensory neurons are unknown [3,4].…”

Alternate metabolism during the dauer stage of the nematode Caenorhabditis elegans

“…The chemical structure of this pheromone has been elucidated recently (Jeong et al, 2005). A build up of this dauer inducing pheromone is the normal physiological trigger for dauer formation.…”