title: A genetic screen for suppressors and enhancers of the Drosophila cdk1-cyclin B identifies maternal factors that regulate microtubule and microfilament stability.
abstract: Coordination between cell-cycle progression and cytoskeletal dynamics is important for faithful transmission of genetic information. In early Drosophila embryos, increasing maternal cyclin B leads to higher Cdk1-CycB activity, shorter microtubules, and slower nuclear movement during cycles 5-7 and delays in nuclear migration to the cortex at cycle 10. Later during cycle 14 interphase of six cycB embryos, we observed patches of mitotic nuclei, chromosome bridges, abnormal nuclear distribution, and small and large nuclei. These phenotypes indicate disrupted coordination between the cell-cycle machinery and cytoskeletal function. Using these sensitized phenotypes, we performed a dosage-sensitive genetic screen to identify maternal proteins involved in this process. We identified 10 suppressors classified into three groups: (1) gene products regulating Cdk1 activities, cdk1 and cyclin A; (2) gene products interacting with both microtubules and microfilaments, Actin-related protein 87C; and (3) gene products interacting with microfilaments, chickadee, diaphanous, Cdc42, quail, spaghetti-squash, zipper, and scrambled. Interestingly, most of the suppressors that rescue the astral microtubule phenotype also reduce Cdk1-CycB activities and are microfilament-related genes. This suggests that the major mechanism of suppression relies on the interactions among Cdk1-CycB, microtubule, and microfilament networks. Our results indicate that the balance among these different components is vital for normal early cell cycles and for embryonic development. Our observations also indicate that microtubules and cortical microfilaments antagonize each other during the preblastoderm stage.
authors.affiliation: Department of Zoology, University of Washington, Seattle 98195-1800, USA.
authors.forename: Jun-Yuan
authors.initials: JY
authors.lastname: Ji
authors.forename: Marjan
authors.initials: M
authors.lastname: Haghnia
authors.forename: Cory
authors.initials: C
authors.lastname: Trusty
authors.forename: Lawrence S B
authors.initials: LS
authors.lastname: Goldstein
authors.forename: Gerold
authors.initials: G
authors.lastname: Schubiger
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics*; D003285:Contractile Proteins; D019926:Cyclin B / Q000235:genetics*; D004330:Drosophila / Q000196:embryology / Q000235:genetics; D029721:Drosophila Proteins; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000235:genetics; D016153:Genes, Suppressor; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D051304:Profilins
chemical_list: D003285:Contractile Proteins; C503698:CycB protein, Drosophila; D019926:Cyclin B; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D051304:Profilins; C495737:chic protein, Drosophila; D016203:CDC2 Protein Kinase