homolog GLP-1 and a Delta-like ligand controls germ-line proliferation in the hermaphrodite. However, since GLP-1 signaling is also essential for early inductions in the embryo, further genetic modification would have to be carried out in order to use the GLP-1 variant of the pathway.

Wnt Pathways. Several recently discovered pathways involving WNT-like ligands and the homologous receptors appear to be important for establishing cell polarities and resulting patterning processes throughout C. elegans development; however, some of these pathways appear to be required only postembryonically and are nonessential for viability (Wood 1998).

Stress Pathways. GFP reporters have been made for various heat-shock proteins of the cytosolic unfolded protein pathway. Because C. elegans is transparent, transgenic animals carrying such reporters could provide a convenient readout of stress-pathway activation in response to toxicants.

Apoptosis Pathway. Much of the current fundamental knowledge of cell-death control was worked out in C. elegans. The pathway of interacting gene products that controls apoptosis during normal C. elegans development is well defined (Metzstein et al. 1998). It is considerably simpler than the pathways that are emerging in mammals, as is true for the simple model organisms in general; therefore, all aspects of the mammalian mechanisms are not represented in C. elegans. For example, there is only one cysteine protease, CED-3, in C. elegans, and there are at least 10 in humans (Salvesen 1999). Nevertheless, the control pathways are fundamentally similar. Sensitized pathways that can be produced by mutations in C. elegans should prove useful in testing for toxicants that cause developmental defects by way of apoptosis. As noted in Chapter 6, a variety of toxicants increase apoptosis in affected rodent embryos.

Behavioral Development Pathways. Although the behavioral repertoire of C. elegans is limited, the neural and molecular bases for several behaviors are well understood in the context of the completely mapped connectivity of its simple nervous system, which includes only 302 neurons. Because these behaviors are easily scored in the laboratory, assays for abnormal development or function of neuronal signaling pathways could provide simple, inexpensive, and useful screens for neurotoxins and other toxicants affecting development.

Genetic analyses have identified over 100 genes required for development of animals with normal movement. The “uncoordinated” (UNC) phenotypes resulting from mutations in these genes can be the consequence of either neuronal or muscular defects (Moerman and Fire 1997; Ruvkun 1997). Assays for toxicant effects on movement could therefore detect interference with the normal development and function of both muscles and the neurons that control them. Moreover,



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