A Reductionist Approach in Gene Screening

Science's STKE  10 May 2005:
Vol. 2005, Issue 283, pp. tw177
DOI: 10.1126/stke.2832005tw177

Cellular signaling pathways, such as Wnt in vertebrates or Wingless in flies, have traditionally been pieced together one step at a time. Technical advances now allow a more thorough probing of the genes whose products contribute to such a regulatory system. DasGupta et al. (see the Perspective by Fearon and Cadigan and Connection Maps of the signaling pathways linked to the online paper) designed a high-throughput screen in Drosophila cells that evaluated effects on Wingless signaling when expression of nearly every gene (about 22,000 of them) was decreased, one by one, by RNA interference. The 238 genes identified included about 15 known components of the signaling pathway. The remaining group comprised approximately equal numbers of genes with known functions not previously associated with Wingless signaling. Half of the implicated genes appear to have orthologs in humans, and a substantial proportion of these human genes show mutations linked to disease.

R. DasGupta, A. Kaykas, R. T. Moon, N. Perrimon, Functional genomic analysis of the Wnt-Wingless signaling pathway. Science 308, 826-833 (2005). [Abstract] [Full Text]

E. R. Fearon, K. M. Cadigan, Wnt signaling glows with RNAi. Science 308, 801-803 (2005). [Summary] [Full Text]