We report here the identification of a novel complementation group in the fruit fly Drosophila melanogaster named gang of four (gfr). Mutations in gfr disrupt patterns of cell differentiation in the eye and increase eye size through a proliferative mechanism that can be enhanced by a block in apoptosis. gfr mutant cells show several features of deregulated Ras/MAP kinase activity, including reduced expression of the Capicua growth suppressing transcription factor and synthetically lethality with alleles of the Jun N-terminal kinase phosphatase puckered. gfr alleles also upreguate Notch activity in the eye. Thus, gfr alleles appear to elicit growth and patterning phenotypes via effects on multiple signaling pathways. Moreover, the gfr alleles behave as gain-of-function lesions and overexpress the gene, bruno-3 (bru-3), which is located at the genomic region to which gfr lesions map. Genetic reduction of bru-3 suppresses phenotypes caused by gfr alleles, and like gfr alleles, overexpression of bru-3 depresses levels of Cic protein, indicating that overexpression of bru-3 is central to gfr mutant phenotypes.