We have utilized C. elegans as a model organism to study alternative splicing regulation in vivo (Nat Meth, 2006; Nat Protoc, 2010). By constructing multi-chromatic alternative splicing reporter mini-genes for C. elegans, we successfully visualized cell-type-specific and developmentally regulated alternative splicing events in vivo (Mol Cell Biol, 2007; Genes Dev, 2008).

As C. elegans is transparent, it is easy to observe expression patterns of multiple fluorescent proteins in living worms at a single cell resolution. Furthermore, a variety of genetic tools for C. elegans research, such as transgenic expression of exogenous proteins, mutant screening and gene mapping, and RNAi-mediated gene knock-down, facilitated further analyses of trans-acting factors and cis-elements, and identification of partially spliced RNA species.

Another advantage of C. elegans in studying splicing regulation is that its introns are on average very short and therefore it is easy to construct reporter mini-genes that include all the required elements.

The studies on splicing regulation in C. elegans revealed that regulation mechanisms of alternative splicing is evolutionarily conserved between nematodes and mammals, and therefore further studies in C. elegans will help determine cellular codes for alternative splicing in higher organisms. Our reporter system will further elucidate expression profiles and regulation mechanisms of alternative splicing in vivo.