The photoreceptor cells R8, R2, and R5 are the first cells to initiate neuronal differentiation in the Drosophila eye imaginal disc. We have shown previously that these three cells require Star gene function for proper ommatidial assembly. Due to the embryonic lethality associated with mutations in Star, we have analyzed the consequence of loss of Star function in mosaic eye imaginal discs. Presumptive R8, R2, and R5 cells that lack Star function fail to differentiate neuronally and die a few hours later. Enhancer trap insertions reveal that Star expression in the eye disc is restricted to the developing R8, R2, and R5 cells. Taken together, these data suggest that Star is required for the reception of a signal and/or the execution of a developmental program that leads to the neuronal differentiation of R8, R2, and R5. Star is also required for the formation of wing veins and is expressed in developing veins, suggesting that at least partially overlapping pathways may operate during photoreceptor cell differentiation and wing vein formation. The role of Star in cell-cell signaling is supported by the observation of genetic interactions between Star and mutations that reduce signaling through both sevenless and the Drosophila EGF-receptor homologue, including Ras1 and Son of sevenless.