a skilled observer can distinguish many different UNC phenotypes associated with specific defects that are genetically and often physiologically understood. Therefore, comparison of toxicant-induced abnormal movement to behavior of known mutants could rapidly provide initial evidence on the point of action of the toxicant.
More specialized assays could be developed based on the animal’s chemosensory abilities. C. elegans normally senses and responds appropriately to a variety of ionic and volatile chemoattractants (e.g., Na+, K+, ethanol, and ketones) and chemorepellants (e.g., acid pH, Cu2+, octanol, and benzaldehyde) in their environment (Bargmann and Mori 1997). These responses are mediated in the head by chemosensory neurons, which send information for control of movement via the major anterior ganglion, called the nerve ring, and the ventral and dorsal nerve cords. Chemoreception involves a large family of 7-membrane-pass cell-surface receptors, which are divergent from chemoreceptors in vertebrates. However, the neurotransmitter receptors (both ligand-gated channels and G-protein linked), neurotransmitter synthesis and release pathways, and G-protein-linked second-messenger pathways involved in chemoresponses are highly conserved between C. elegans and mammals (Bargmann 1998). Extensive genetic and neuron ablation studies have shown that defects in the development of these signaling pathways lead to abnormal chemosensory responses, which are easily and inexpensively assayed on agar plates in the laboratory.
Another potentially informative assay system could be based on the C. elegans dauer pathway. The dauer (enduring) larva is a state of diapause that allows a population to survive periods of limited food and overcrowding. Under such conditions, the animals produce a pheromone that can be detected by sensory neurons in the head. Presence of the pheromone induces molting of L2 larvae (see Figure 7-1) to an alternative form of the L3 larva called the dauer larva or simply dauer, which is resistant to dessication, does not feed, and has a low metabolic rate and an increased lifespan of several months compared with the normal lifespan of about 2 weeks. This response is mediated by a signaling pathway that is clearly homologous to the metabolically crucial pathway of insulin signaling in mammals. Genetic analysis has identified components of the pathway that are required for dauer formation under starvation conditions, as well as components required for preventing dauer formation when food is available (Riddle and Albert 1997). Defective function of either class of components is easily assayed in the laboratory.
Not only could such assays serve as the basis for testing toxicant effects on nervous system development and function, but also the extensive knowledge of the cells and molecules involved should make it possible to rapidly identify the components affected by a toxicant that causes behavioral defects.