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Genetics, Vol. 149, 1867-1882, August 1998, Copyright © 1998

Analysis of a Drosophila cyclin E Hypomorphic Mutation Suggests a Novel Role for Cyclin E in Cell Proliferation Control During Eye Imaginal Disc Development

Julie Secombea, Johanna Pispab, Robert Sainta, and Helena Richardsona
a Department of Genetics, University of Adelaide, South Australia, Australia, 5005
b Center of Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, New York 10032

Corresponding author: Helena Richardson, Department of Genetics, University of Adelaide, South Australia, Australia, 5005., herichardson{at}gina.science.adelaide.edu.au (E-mail).

Communicating editor: K. ANDERSON

We have generated and characterized a Drosophila cyclin E hypomorphic mutation, DmcycEJP, that is homozygous viable and fertile, but results in adults with rough eyes. The mutation arose from an internal deletion 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 eye imaginal disc development. Eye imaginal discs from DmcycEJP larvae contain fewer S phase cells, both anterior and posterior to the morphogenetic 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 p21CIP1 homolog dacapo, which encode proteins known to physically interact with Cyclin E, modified the DmcycEJP rough eye phenotype as expected. Decreasing the dosage of the S phase transcription factor gene, dE2F, enhanced the DmcycEJP rough eye phenotype. Surprisingly, mutations in G2/M phase regulators cyclin A and string (cdc25), but not cyclin B1, B3, or cdc2, enhanced the DmcycEJP phenotype without affecting the number of cells entering S phase, but by decreasing the number of cells entering mitosis. Our analysis establishes the DmcycEJP allele as an excellent resource for searching for novel cyclin E genetic interactors. In addition, this analysis has identified cyclin A and string as DmcycEJP interactors, suggesting a novel role for cyclin E in the regulation of Cyclin A and String function during eye development.




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