A genomic survey uses innovative genetics to make neurons susceptible to RNA-mediated gene inactivation. The results implicate many genes in communication at the synapse between neurons and muscle. RNA interference (RNAi) is a spectacularly useful technique for selectively reducing gene activity ― and thereby garnering clues about gene function1. In this issue, a collaborative group of geneticists, genomicists and neuro-scientists report the first large-scale RNAi screen in neuroscience (Sieburth et al, page 510). They identify more than 100 novel genes that have specific functions in the transmission of signals across the junction between neurons and muscle cells. The nematode worm Caenorhabditis ele-gans was the subject of the first genome-wide RNAi screens, aimed at finding the genes involved in development. But neurons in C. elegans have proved inexplicably resistant to the technique. The Ruvkun lab has taken the geneticists gambit to solve this problem: if you want something but have no idea how to get it, just find the right mutant. Their clever two-step screen to look for such mutants yielded a strain, designated eri-l; lin-15B, in which neuronal RNAi is possible.
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