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Cellular signaling pathways such as the Wnt/Wingless pathway have traditionally been pieced together one step at a time. In a Perspective, Fearon and Cadigan discuss a new high-throughput screen in fruit fly cells that blocks the activity of nearly all fruit fly genes, one by one ( DasGupta et al. ). This study reveals 238 components of the Wnt/ Wingless pathway, including several proteins not previously known to operate in this pathway.