Advertisement
JOURNAL ARTICLES
The Drosophila gene morula inhibits mitotic functions in the endo cell cycle and the mitotic cell cycle
B.H. Reed, T.L. Orr-Weaver
Development 1997 124: 3543-3553;

Summary

In the endo cell cycle, rounds of DNA replication occur in the absence of mitosis, giving rise to polyploid or polytene cells. We show that the Drosophila morula gene is essential to maintain the absence of mitosis during the endo cycle. During oogenesis in wild-type Drosophila, nurse cells become polyploid and do not contain cyclin B protein. Nurse cells in female-sterile alleles of morula begin to become polyploid but revert to a mitotic-like state, condensing the chromosomes and forming spindles. In strong, larval lethal alleles of morula, the polytene ring gland cells also inappropriately regress into mitosis and form spindles. In addition to its role in the endo cycle, morula function is necessary for dividing cells to exit mitosis. Embryonic S-M cycles and the archetypal (G1-S-G2-M) cell cycle are both arrested in metaphase in different morula mutants. These phenotypes suggest that morula acts to block mitosis-promoting activity in both the endo cycle and at the metaphase/anaphase transition of the mitotic cycle. Consistent with this, we found cyclin B protein to be inappropriately present in morula mutant nurse cells. Thus morula serves a dual function as a cell cycle regulator that promotes exit from mitosis and maintains the absence of mitosis during the endo cycle, possibly by activating the cyclin destruction machinery.

REFERENCES

    1. Aggarwal S. K.,
    2. King R. C.
    (1969) A comparative study of the ring glands from wild type and l(2)gl mutant Drosophila melanogaster. J. Morph 129, 171–200
    OpenUrlCrossRefPubMed
    1. Amon A.,
    2. Irniger S.,
    3. Nasmyth K.
    (1994) Closing the cell cycle circle in yeast: G2 cyclin proteolysis initiated at mitosis persists until the activation of G1 cyclins in the next cycle. Cell 77, 1037–1050
    OpenUrlCrossRefPubMedWeb of Science
    1. Chou T.-B.,
    2. Perrimon N.
    (1992) Use of a yeast site-specific recombinase to produce female germline chimeras in Drosophila. Genetics 131, 643–653
    OpenUrlAbstract/FREE Full Text
    1. Chou T.-B.,
    2. Perrimon N.
    (1996) The autosomal FLP-DFS technique for generating germline mosaics in Drosophila melanogaster. Genetics 144, 1673–1679
    OpenUrlAbstract/FREE Full Text
    1. Cohen-Fix O.,
    2. Peters J.-M.,
    3. Kirschner M. W.,
    4. Koshland D.
    (1996) Anaphase initiation in Saccharomyces cerevisiae is controlled by the APC-dependent degradation of the anaphase inhibitor Pds1p. Genes Dev 10, 3081–3093
    OpenUrlAbstract/FREE Full Text
    1. Dalby B.,
    2. Glover D. M.
    (1992) 3non-translated sequences in Drosophila cyclin B transcripts direct posterior pole accumulation late in oogenesis and per-nuclear association in syncytial embryos. Development 115, 989–997
    OpenUrlAbstract
    1. Dawson I. A.,
    2. Roth S.,
    3. Akam M.,
    4. Artavanis-Tsakonas S.
    (1993) Mutations at the fizzy locus cause metaphase arrest in Drosophila melanogaster embryos. Development 117, 359–376
    OpenUrlAbstract/FREE Full Text
    1. Dawson I. A.,
    2. Roth S.,
    3. Artavanis-Tsakonas S.
    (1995) The Drosophila cell cycle gene fizzy is required for normal degradation of cyclins A and B during mitosis and has homology to the CDC20 gene of Saccharomyces cerevisiae. J. Cell Biol 129, 725–737
    OpenUrlAbstract/FREE Full Text
    1. Duronio R. J.,
    2. O'Farrell P. H.
    (1994) Developmental control of a G1-S transcriptional program in Drosophila. Development 120, 1503–1515
    OpenUrlAbstract
    1. Duronio R. J.,
    2. O'Farrell P. H.,
    3. Xie J.-E.,
    4. Brook A.,
    5. Dyson N.
    (1995) The transcription factor E2F is required for S phase during Drosophila embryogenesis. Genes Dev 9, 1445–1455
    OpenUrlAbstract/FREE Full Text
    1. Funabiki H.,
    2. Yamano H.,
    3. Kumada K.,
    4. Nagao K.,
    5. Hunt T.,
    6. Yanagida M.
    (1996) Cut2 proteolysis required for sister-chromatid separation in fission yeast. Nature 381, 438–441
    OpenUrlCrossRefPubMedWeb of Science
    1. Gatti M.,
    2. Baker B.
    (1989) Genes controlling essential cell-cycle functions in Drosophila melanogaster. Genes Dev 3, 438–453
    OpenUrlAbstract/FREE Full Text
    1. Gatti M.,
    2. Goldberg M. L.
    (1991) Mutations affecting cell division in Drosophila. Methods in Cell Biology 35, 543–586
    OpenUrlCrossRefPubMed
    1. Glotzer M.,
    2. Murray A. W.,
    3. Kirschner M. W.
    (1991) Cyclin is degraded by the ubiquitin pathway. Nature 349, 132–138
    OpenUrlCrossRefPubMedWeb of Science
    1. Hayashi S.
    (1996) A cdc2 dependent checkpoint maintains diploidy in Drosophila. Development 122, 1051–1058
    OpenUrlAbstract
    1. Holloway S. L.,
    2. Glotzer M.,
    3. King R. W.,
    4. Murray A. W.
    (1993) Anaphase is initiated by proteolysis rather than by the inactivation of maturation-promoting factor. Cell 73, 1393–1402
    OpenUrlCrossRefPubMedWeb of Science
    1. Irniger S.,
    2. Piatti S.,
    3. Michaelis C.,
    4. Nasmyth K.
    (1995) Genes involvedin sister chromatid separation are needed for B-type cyclin proteolysis in budding yeast. Cell 81, 269–277
    OpenUrlCrossRefPubMedWeb of Science
    1. James S. W.,
    2. Mirabito P. M.,
    3. Scacheri P. C.,
    4. Morris N. R.
    (1995) The Aspergillus nidulans bimE (b locked- i n- m itosis) gene encodes multiple cell cycle functions involved in mitotic checkpoint control and mitosis. J. Cell Sci 108, 3485–3499
    OpenUrlAbstract/FREE Full Text
    1. King R. C.
    (1959) Oogenesis in mr2. Drosophila Information Service 33, 143–.
    OpenUrl
    1. King R. C.,
    2. Aggarwal S. K.,
    3. Bodenstein D.
    (1966) The comparative submicroscopic morphology of the ring gland of Drosophila melanogaster during the second and third larval instars. Zeitschrift fur Zellforschung 73, 272–285
    OpenUrlCrossRefPubMed
    1. King R. W.,
    2. Peters J.-M.,
    3. Tugendreich S.,
    4. Rolfe M.,
    5. Hieter P.,
    6. Kirschner M. W.
    (1995) A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B. Cell 81, 279–288
    OpenUrlCrossRefPubMedWeb of Science
    1. King R. W.,
    2. Deshaies R. J.,
    3. Peters J.-M.,
    4. Kirschner M. W.
    (1996) How proteolysis drives the cell cycle. Science 274, 1652–1659
    OpenUrlAbstract/FREE Full Text
    1. Knoblich J. A.,
    2. Sauer K.,
    3. Jones L.,
    4. Richardson H.,
    5. Saint R.,
    6. Lehner C. F.
    (1994) Cyclin E controls S phase progression and its down-regulation during Drosophila embryogenesis is required for the arrest of cell proliferation. Cell 77, 107–120
    OpenUrlCrossRefPubMedWeb of Science
    1. Kose H.,
    2. Karr T. L.
    (1995) Organization of Wolbachia pipientis in the Drosophila fertilized egg and embryo revealed by an anti-Wolbachia monoclonal antibody. Mechan. Dev 51, 275–288
    OpenUrlCrossRefPubMedWeb of Science
    1. Lasko P. F.,
    2. Ashburner M.
    (1990) Posterior localization of vasa protein correlates with, but is not sufficient for, pole cell development. Genes Dev 4, 905–921
    OpenUrlAbstract/FREE Full Text
    1. Lees A. D.,
    2. Waddington C. H.
    (1942) The development of the bristles in normal and some mutant types of Drosophila melanogaster. Proc. Royal Soc. London Series B 131, 87–110
    OpenUrlAbstract/FREE Full Text
    1. Lehner C. F.,
    2. O'Farrell P. H.
    (1989) Expression and function of Drosophila cyclin A during embryonic cell cycle progression. Cell 56, 957–968
    OpenUrlCrossRefPubMedWeb of Science
    1. Lehner C. F.,
    2. O'Farrell P. H.
    (1990) The roles of Drosophila cyclins A and B in mitotic control. Cell 61, 535–547
    OpenUrlCrossRefPubMedWeb of Science
    1. Lilly M. A.,
    2. Spradling A. C.
    (1996) The Drosophila endocycle is controlled by Cyclin E and lacks a checkpoint ensuring S-phase completion. Genes Dev 10, 2514–2526
    OpenUrlAbstract/FREE Full Text
    1. Lynch C. J.
    (1919) An analysis of certain cases of intra-specific sterility. Genetics 4, 501–523
    OpenUrlFREE Full Text
    1. Mahowald A. P.,
    2. Strassheim J. M.
    (1970) Intercellular migration of centrioles in the germarium of Drosophila melanogaster. J. Cell Biol 45, 306–320
    OpenUrlAbstract/FREE Full Text
    1. Oegema K.,
    2. Whitfield W. G.,
    3. Alberts B.
    (1995) The cell cycle-dependent localization of the CP190 centrosomal protein is determined by the coordinate action of two separable domains. J. Cell Biol 131, 1261–1273
    OpenUrlAbstract/FREE Full Text
    1. Osmani S. A.,
    2. Engle D. B.,
    3. Doonan J. H.,
    4. Morris N. R.
    (1988) Spindle formation and chromatin condensation in cells blocked at interphase by mutation of a negative cell cycle control gene. Cell 52, 241–251
    OpenUrlCrossRefPubMedWeb of Science
    1. Osmani A. H.,
    2. O'Donnell K.,
    3. Pu R. T.,
    4. Osmani S. A.
    (1991) Activation of the nim A protein kinase plays a unique role during mitosis thatcannot be bypassed by absence of the bim E checkpoint. EMBO J 10, 2669–2679
    OpenUrlPubMedWeb of Science
    1. Page A. W.,
    2. Orr-Weaver T. L.
    (1996) The Drosophila genes grauzone and cortex are necessary for proper female meiosis. J. Cell Sci 109, 1707–1715
    OpenUrlAbstract/FREE Full Text
    1. Peters J.-M.,
    2. King R. W.,
    3. Hoog C.,
    4. Kirschner M. W.
    (1996) Identification of BIME as a subunit of the anaphase-promoting complex. Science 274, 1199–1201
    OpenUrlAbstract/FREE Full Text
    1. Ribbert D.
    (1979) Chromomeres and puffing in experimentally induced polytene chromosomes of Calliphora erythrocephala. Chromosoma 74, 269–298
    OpenUrlCrossRefPubMedWeb of Science
    1. Sauer K.,
    2. Knoblich J. A.,
    3. Richardson H.,
    4. Lehner C. F.
    (1995) Distinct modes of cyclin E/cdc2c kinase regulation and S-phase control in mitotic and endoreduplication cycles of Drosophila embryogenesis. Genes Dev 9, 1327–1339
    OpenUrlAbstract/FREE Full Text
    1. Sigrist S.,
    2. Jacobs H.,
    3. Stratmann R.,
    4. Lehner C. F.
    (1995) Exit from mitosis is regulated by Drosophila fizzy and the sequential destruction of cyclins A, B, and B3. EMBO J 14, 4827–4838
    OpenUrlPubMedWeb of Science
    1. Smith A. V.,
    2. Orr-Weaver T. L.
    (1991) The regulation of the cell cycle during Drosophila embryogenesis: the transition to polyteny. Development 112, 997–1008
    OpenUrlAbstract
    1. Stern B.,
    2. Ried G.,
    3. Clegg N.,
    4. Grigliatti T.,
    5. Lehner C.
    (1993) Genetic analysis of the Drosophila cdc2 homolog. Development 117, 219–232
    OpenUrlAbstract/FREE Full Text
    1. Sudakin V.,
    2. Ganoth D.,
    3. Dahan A.,
    4. Heller H.,
    5. Hershko J.,
    6. Luca F. C.,
    7. Ruderman J. V.,
    8. Hershko A.
    (1995) The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis. Mol. Biol. Cell 6, 185–198
    OpenUrlAbstract/FREE Full Text
    1. Surana U.,
    2. Amon A.,
    3. Dowzer C.,
    4. McGrew J.,
    5. Byers B.,
    6. Nasmyth K.
    (1993) Destruction of the CDC28 / CLB mitotic kinase is not required for the metaphase to anaphase transition in budding yeast. EMBO J 12, 1969–1978
    OpenUrlPubMedWeb of Science
    1. Theurkauf W. E.,
    2. Smiley S.,
    3. Wong M. L.,
    4. Alberts B. M.
    (1992) Reorganization of the cytoskeleton during Drosophila oogenesis: implications for axis specification and intercellular transport. Development 115, 923–936
    OpenUrlAbstract
    1. Waddington C. H.,
    2. Pilkington R. W.
    (1943) The structure and development of four mutant eyes in Drosophila. J. Genetics 45, 44–50
    OpenUrl
    1. Whitfield W.,
    2. Gonzalez C.,
    3. Maldonado-Codina G.,
    4. Glover D.
    (1990) The A-and B-type cyclins of Drosophila are accumulated and destroyed in temporally distinct events that define separable phases of the G2-M transition. EMBO J 9, 2563–2572
    OpenUrlPubMedWeb of Science
    1. Zachariae W.,
    2. Shin T. H.,
    3. Galova M.,
    4. Obermaier B.,
    5. Nasmyth K.
    (1996) Identification of subunits of the anaphase-promoting complex of Saccharomyces cerevisiae. Science 274, 1201–1204
    OpenUrlAbstract/FREE Full Text
Back to top

 Download PDF

Email
JOURNAL ARTICLES
The Drosophila gene morula inhibits mitotic functions in the endo cell cycle and the mitotic cell cycle
B.H. Reed, T.L. Orr-Weaver
Development 1997 124: 3543-3553;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Alerts

Article navigation

Other journals from The Company of Biologists

Advertisement

A new society for regenerative biologists

Kenneth Poss and Elly Tanaka announce the launch of the International Society for Regenerative Biology (ISRB), which will promote research and education in the field of regenerative biology.

Upcoming special issue: call for papers

The Immune System in Development and Regeneration
Guest editors: Florent Ginhoux and Paul Martin
Submission deadline: 1 September 2021
Publication: Spring 2022

The special issue welcomes Review articles as well as Research articles, and will be widely promoted online and at key global conferences.

An interview with Cagney Coomer

Over a virtual chat, we spoke to Cagney Coomer about her experiences in the lab, the classroom and the community centre, and why she thinks outreach and role models are vital to science.

Development presents...

Our successful webinar series continues into 2021, with early-career researchers presenting their papers and a chance to virtually network with the developmental biology community afterwards. Here, Michèle Romanos talks about her new preprint, which mixes experimentation in quail embryos and computational modelling to understand how heterogeneity in a tissue influences cell rate.

Save your spot at our next session:

10 March
Time: 9:00 (GMT)
Chaired by: Thomas Lecuit

Join our mailing list to receive news and updates on the series.