Dominant effects of the bcr-abl oncogene on Drosophila morphogenesis

We targeted expression of human/fly chimeric Bcr-Abl proteins to the develo ping central nervous system (CNS) and eye imaginal disc of Drosophila melan ogaster, Neural expression of human/fly chimeric P210 Bcr-Abl or P185 Bcr-A bl rescued abl mutant flies from pupal lethality, indicating that P210 and P185 Bcr-Abl can substitute functionally for Drosophila Abl during axonogen esis, However, increased levels of neurally expressed P210 or P185 Bcr-Abl but not Drosophila Abl produced CNS defects and lethality. Expression of P2 10 or P185 in the eye imaginal disc produced a dominant rough eye phenotype that was dependent on dosage of the transgene. Drosophila Enabled, previou sly identified as a suppressor of the abl mutant phenotype and substrate fo r Drosophila Abl kinase, had markedly increased phosphotyrosine levels in B cr-Abl expressing Drosophila, indicating that it is a substrate for Bcr-Abl as well, Drosophila, therefore, is a suitable model system to identify Bcr -Abl interactions important for signal transduction and oncogenesis.