ANALYSIS OF A DROSOPHILA CYCLIN-E HYPOMORPHIC MUTATION SUGGESTS A NOVEL ROLE FOR CYCLIN-E IN CELL-PROLIFERATION CONTROL DURING EYE IMAGINALDISC DEVELOPMENT

We have generated and characterized a Drosophila cyclin E hypomorphic mutation, DmcycE(JP), that is homozygous viable and fertile, but resul ts in adults with rough eyes. The mutation arose from an internal dele tion of an existing P[w(+)lacZ] element inserted 14 kb upstream of the transcription start site of the DmcycE zygotic mRNA. The presence of this deleted P element, but not the P[w(+)lacZ] element from which it was derived, leads to a decreased level of DmcycE expression during ey e imaginal disc development. Eye imaginal discs from DmcycE(JP) larvae contain fewer S phase cells, both anterior and posterior to the morph ogenetic furrow. This results in adults with small rough eyes, largely due to insufficient numbers of pigment cells. Altering the dosage of the Drosophila cdk2 homolog, cdc2c, retinoblastoma, or p21(CIP1) homol og dacapo, which encode proteins known to physically interact with Cyc lin E, modified the DmcycE(JP) rough eye phenotype as expected. Decrea sing the dosage of the S phase transcription factor gene, dE2F, enhanc ed the DmcycE(JP) rough eye phenotype. Surprisingly, mutations in G2/M phase regulators cyclin A and string (cdc25), but not cyclin B1, B3, or cdc2 enhanced the DmcycE(JP) phenotype without affecting the number of cells entering S phase, but by decreasing the number of cells ente ring mitosis. Our analysis establishes the DmcycE(JP) allele as an exc ellent resource for searching for novel cyclin E genetic interactors. In addition, this analysis has identified cyclin A and string as Dmcyc E(JP) interactors, suggesting a novel role for cyclin E in the regulat ion of Cyclin A and String function during eye development.