Screen overview. (A) A genome-wide morphology RNAi screen was performed in Drosophila S2R+ cells and in a subset of human HeLa cells for genes corresponding to a comprehensive set of all known human actin regulatory genes and genes predicted to play a role based on their domain structure. Comparing the two screens we were able to cluster the hits into morphological groups and arrive at a shortlist of conserved known and new actin regulatory genes. (B) A flowchart of the methodology. (C) Breakdown of all Drosophila hits by dominant phenotype; many hits fell into multiple categories, but these have only been accounted for in one category in this graph (see Table S2 for details). (D) Fly and (E) human hits clustered as a heat map; red indicates a hit in the specified category.