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 Secombe, Johanna Pispa, Robert Saint, Helena Richardson

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

We have generated and characterized a Drosophila cyclin E hypomorphic mutation, DmcycE(JP), 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 DmcycE(JP) 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 p21(CIPI) homolog dacapo, which encode proteins known to physically interact with Cyclin E, modified the DmcycE(JP) rough eye phenotype as expected. Decreasing the dosage of the S phase transcription factor gene, dE2F, enhanced 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 entering mitosis. Our analysis establishes the DmcycE(JP) allele as an excellent resource for searching for novel cyclin E genetic interactors. In addition, this analysis has identified cyclin A and string as DmcycE(JP) interactors, suggesting a novel role for cyclin E in the regulation of Cyclin A and String function during eye development.

Original languageEnglish (US)
Pages (from-to)1867-1882
Number of pages16
JournalGenetics
Volume149
Issue number4
StatePublished - Aug 1998
Externally publishedYes

Fingerprint

Imaginal Discs
Cyclin E
Drosophila
Cell Proliferation
Mutation
Cyclin A
S Phase
Cell Count
Phenotype
Cyclin B1
Retinoblastoma
G2 Phase
Transcription Initiation Site
Mitosis
Cell Division
Larva
Transcription Factors
Alleles
Messenger RNA

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Analysis of a Drosophila cyclin E hypomorphic mutation suggests a novel role for cyclin E in cell proliferation control during eye imaginal disc development. / Secombe, Julie; Pispa, Johanna; Saint, Robert; Richardson, Helena.

In: Genetics, Vol. 149, No. 4, 08.1998, p. 1867-1882.

Research output: Contribution to journalArticle

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