reverse genetics using RNAi, its anatomical and developmental simplicity, and its transparency throughout the life cycle, allowing visualization of internal phenotypes at the cellular level and expression of fluorescent reporters, such as GFP, in living specimens. One possible disadvantage is that, as a soil organism, it might have evolved resistances to some chemicals that can act as developmental toxicants in higher animals. These differences could in principle be characterized and genetically modified. Another possible disadvantage is that its collagenous cuticle might be impermeable to many test compounds. However, since larvae and adults constantly ingest materials from their environment, compounds that are not rapidly degraded should enter the animal through the gut.
Many of the signaling pathways described in Chapter 6 have now been demonstrated to function in C. elegans development. Of particular potential utility for toxicological applications are pathways important for postembryonic development but not essential for viability up to that point, so they can be assayed in living animals. A few examples of such pathways follow. For some, sensitized strains are already available; for the others, they can be easily constructed.
Receptor Tyrosine Kinase (RTK) Pathways. One of the best-studied signaling pathways is not essential for viability in C. elegans but does mediate the induction of the hermaphrodite vulva in the hypodermis. The gonadal anchor cell releases an epidermal-growth-factor-like signal to nearby hypodermal cells that receive it via an appropriate RTK and the downstream components of a typical Ras signaling pathway. Defects in this pathway lead to an easily visible lack of a vulva (and, hence, inability to lay eggs) or to multiple vulva-like structures (Sternberg and Horvitz 1991). This organogenesis operates in the last larval stage, when the animal feeds actively. Sensitized strains for screens for enhancer and suppressor mutations are already available and could be used to test for effects of toxicants on pathway function.
Transforming-Growth-Factor (TGF) β Pathways. Also nonessential for larval viability are two distinct pathways responding to different TGFβ-superfamily ligands, which interact via receptor serine and threonine kinases with typical downstream Smad protein components. One is involved in controlling development of C. elegans larvae into a diapause form (the dauer larva) under adverse conditions, and the other is in control of body size and patterning of the tail of the male (Riddle and Albert 1997; Padgett et al. 1998; Suzuki et al. 1999).
Notch and Delta Pathways. Pathways involving the Notch-like receptor LIN-12 and a Delta-like ligand, also nonessential for larval viability, affect postembryonic gonadal and vulval development. Another pathway involving the Notch