ABSTRACT

Caenorhabditis elegans is a nematode worm comprising approximately 900 cells. Its life cycle is short (about 60 h) and culture conditions are very simple. In addition, cell lineage has been extensively characterized (Brenner, 1974; Sulston, 2003; Sulston and Horvitz, 1977; Sulston et al., 1983). Together, these characteristics made C. elegans an organism of choice for genetic and developmental studies (Brenner, 1974). Furthermore, across the years, large collections of mutations in its genome have made this organism one of the most amenable systems for such genetic analyses. In 1998, the C. elegans genome was the first metazoan genome to be completely sequenced (https://www.sanger.ac.uk/Projects/C_elegans/) (C. elegans Sequencing Consortium, 1998) and this initiative allowed for the generation of resource functional tools such as the C. elegans ORFeome (Reboul et al., 2003). These genomic studies were recently utilized to provide the first metazoan protein-protein interaction map (Li et al., 2004).

RNAi was discovered several years ago following the observation that the introduction of dsRNA caused the specific degradation of mRNA. This was particularly true in C. elegans (Guo and Kemphues, 1995) and it was soon recognized as experimentally and technically simple to knock down genes in this organism and other species. Subsequently, it was systematically demonstrated that dsRNA is a potent effector of gene interference (Fire et al., 1998). Although RNAi in C. elegans is a powerful method for the inactivation of gene function, it does have several limitations such as tissue-and gene-specific differences in sensitivity to RNAi (Tavernarakis et al., 2000). In addition, it should always be considered that significant inter-experimental variability in RNAi may occur, most likely due to subtle differences in experimental conditions (Simmer et al., 2003).