Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Cycling through development in Drosophila and other metazoa

Nature Cell Biology volume 3, pages E35–E39 (2001)Cite this article

Abstract

The cell-division cycle is an orchestrated sequence of events that results in the duplication of a cell. In metazoa, cell proliferation is regulated in response to differentiation signals and body-size parameters, which either induce cell duplication or arrest the cell cycle, to ensure that organs develop to the correct size. In addition, the cell cycle may be altered to meet specialized requirements. This can be seen in the rapid cleavage cycles of vertebrates and insects that lack gap phases, in the nested S phases of Drosophila , and in the endocycles of nematodes, insects, plants and mammals that lack mitosis. Here we present the various modes of cell-cycle regulation in metazoa and discuss their possible generation by a combination of universally conserved molecules and new regulatory circuits.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Different modes of cell-cycle regulation in yeast and Drosophila .

Similar content being viewed by others

References

  1. Hartenstein, V. & Posakony, J. W. Sensillum development in the absence of cell division: the sensillum phenotype of the Drosophila mutant string. Dev. Biol. 138 , 147–158 (1990).

    Article  CAS  PubMed  Google Scholar 

  2. Fay, D. S. & Han, M. Mutations in cye-1, a Caenorhabditis elegans cyclin E homolog, reveal coordination between cell-cycle control and vulval development. Development 127, 4049–4060 (2000).

    CAS  PubMed  Google Scholar 

  3. Cui, X. & Doe, C. Q. The role of the cell cycle and cytokinesis in regulating neuroblast sublineage gene expression in the Drosophila CNS. Development 121, 3233– 3243 (1995).

    CAS  PubMed  Google Scholar 

  4. Weigmann, K. & Lehner, C. F. Cell fate specification by even-skipped expression in the Drosophila nervous system is coupled to cell cycle progression. Development 121 , 3713–3721 (1995).

    CAS  PubMed  Google Scholar 

  5. Ambros, V. Cell cycle-dependent sequencing of cell fate decisions in Caenorhabditis elegans vulva precursor cells. Development 126, 1947–1956 (1999).

    CAS  PubMed  Google Scholar 

  6. Chenn, A. & McConnell, S. K. Cleavage orientation and the asymmetric inheritance of Notch1 immunoreactivity in mammalian neurogenesis . Cell 82, 631–641 (1995).

    Article  CAS  PubMed  Google Scholar 

  7. Lu, B., Jan, L. Y. & Jan, Y. N. Asymmetric cell division: lessons from flies and worms . Curr. Opin. Genet. Dev. 8, 392– 399 (1998).

    Article  CAS  PubMed  Google Scholar 

  8. Bowerman, B. & Shelton, C. A. Cell polarity in the early Caenorhabditis elegans embryo. Curr. Opin. Genet. Dev. 9, 390–395 ( 1999).

    Article  CAS  PubMed  Google Scholar 

  9. Serrano, N. & O'Farrell, P. H. Limb morphogenesis: connections between patterning and growth. Curr. Biol. 7, R186–R195 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kipreos, E. T., Lander, L. E., Wing, J. P., He, W. W. & Hedgecock, E. M. cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family. Cell 85, 829–839 (1996).

    Article  CAS  PubMed  Google Scholar 

  11. Dong, X. et al. Control of G1 in the developing Drosophila eye: rca1 regulates Cyclin A. Genes Dev. 11, 94–105 (1997).

    Article  CAS  PubMed  Google Scholar 

  12. Horsfield, J., Penton, A., Secombe, J., Hoffman, F. M. & Richardson, H. decapentaplegic is required for arrest in G1 phase during Drosophila eye development . Development 125, 5069– 5078 (1998).

    CAS  PubMed  Google Scholar 

  13. Johnston, L. A. & Edgar, B. A. Wingless and Notch regulate cell-cycle arrest in the developing Drosophila wing . Nature 394, 82–84 (1998).

    Article  CAS  PubMed  Google Scholar 

  14. Mata, J., Curado, S., Ephrussi, A. & Rorth, P. Tribbles coordinates mitosis and morphogenesis in Drosophila by regulating string/CDC25 proteolysis. Cell 101, 511– 522 (2000).

    Article  CAS  PubMed  Google Scholar 

  15. Grosshans, J. & Wieschaus, E. A genetic link between morphogenesis and cell division during formation of the ventral furrow in Drosophila. Cell 101, 523– 531 (2000).

    Article  CAS  PubMed  Google Scholar 

  16. Seher, T. C. & Leptin, M. Tribbles, a cell-cycle brake that coordinates proliferation and morphogenesis during Drosophila gastrulation. Curr. Biol. 10, 623– 629 (2000).

    Article  CAS  PubMed  Google Scholar 

  17. Traas, J., Hulskamp, M., Gendreau, E. & Hofte, H. Endoreduplication and development: rule without dividing? Curr. Opin. Plant Biol. 1, 498–503 (1998).

    Article  CAS  PubMed  Google Scholar 

  18. Flemming, A. J., Shen, Z., Z., Cunha, A., Emmons, S. W. & Leroi, A. M. Somatic polyploidization and cellular proliferation drive body size evolution in nematodes. Proc. Natl Acad. Sci. USA 97, 5285– 5290 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Royzman, I. & Orr-Weaver, T. L. S phase and differential DNA replication during Drosophila oogenesis. Genes Cells 3, 767–776 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  20. Forsburg, S. L. & Nurse, P. Cell cycle regulation in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe . Annu. Rev. Cell Biol. 7, 227– 256 (1991).

    Article  CAS  PubMed  Google Scholar 

  21. Schmelzle, T. & Hall, M. N. TOR, a central controller of cell growth. Cell 103, 253– 262 (2000).

    Article  CAS  PubMed  Google Scholar 

  22. Polymenis, M. & Schmidt, E. V. Coupling of cell division to cell growth by translational control of the G1 cyclin CLN3 in yeast. Genes Dev. 11, 2522– 2531 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Danaie, P., Altmann, M., Hall, M. N., Trachsel, H. & Helliwell, S. B. CLN3 expression is sufficient to restore G1-to-S-phase progression in Saccharomyces cerevisiae mutants defective in translation initiation factor eIF4E. Biochem. J. 340, 135–141 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Russell, P. & Nurse, P. cdc25+ functions as an inducer in the mitotic control of fission yeast. Cell 45, 145–153 (1986).

    Article  CAS  PubMed  Google Scholar 

  25. Thuriaux, P., Nurse, P. & Carter, B. Mutants altered in the control co-ordinating cell division with cell growth in the fission yeast Schizosaccharomyces pombe. Mol. Gen. Genet. 161, 215–220 (1978).

    CAS  PubMed  Google Scholar 

  26. Sveiczer, A., Novak, B. & Mitchison, J. M. The size control of fission yeast revisited. J. Cell Sci. 109, 2947–2957 (1996).

    CAS  PubMed  Google Scholar 

  27. Edgar, B. A. & Lehner, C. F. Developmental control of cell cycle regulators: a fly's perspective. Science 274, 1646–1652 (1996).

    Article  CAS  PubMed  Google Scholar 

  28. Britton, J. S. & Edgar, B. A. Environmental control of the cell cycle in Drosophila: nutrition activates mitotic and endoreplicative cells by distinct mechanisms. Development 125, 2149–2158 (1998).

    CAS  PubMed  Google Scholar 

  29. Neufeld, T. P., de la Cruz, A. F., Johnston, L. A. & Edgar, B. A. Coordination of growth and cell division in the Drosophila wing. Cell 93, 1183– 1193 (1998).

    Article  CAS  PubMed  Google Scholar 

  30. Prober, D. A. & Edgar, B. A. Ras1 promotes cellular growth in the Drosophila wing. Cell 100, 435–446 (2000).

    Article  CAS  PubMed  Google Scholar 

  31. Johnston, L. A., Prober, D. A., Edgar, B. A., Eisenman, R. N. & Gallant, P. Drosophila myc regulates cellular growth during development. Cell 98, 779–790 (1999).

    Article  CAS  PubMed  Google Scholar 

  32. Edgar, B. A. & Datar, S. A. Zygotic degradation of two maternal Cdc25 mRNAs terminates Drosophila's early cell cycle program. Genes Dev. 10, 1966– 1977 (1996).

    Article  CAS  PubMed  Google Scholar 

  33. Clurman, B. E., Sheaff, R. J., Thress, K., Groudine, M. & Roberts, J. M. Turnover of cyclin E by the ubiquitin–proteasome pathway is regulated by cdk2 binding and cyclin phosphorylation. Genes Dev. 10, 1979 –1990 (1996).

    Article  CAS  PubMed  Google Scholar 

  34. Bernardi, R., Liebermann, D. A. & Hoffman, B. Cdc25A stability is controlled by the ubiquitin–proteasome pathway during cell cycle progression and terminal differentiation. Oncogene 19, 2447–2454 ( 2000).

    Article  CAS  PubMed  Google Scholar 

  35. Lehman, D. A. et al. Cis-regulatory elements of the mitotic regulator, string/Cdc25 . Development 126, 1793– 1803 (1999).

    CAS  PubMed  Google Scholar 

  36. Jones, L., Richardson, H. & Saint, R. Tissue-specific regulation of cyclin E transcription during Drosophila melanogaster embryogenesis. Development 127, 4619–4630 ( 2000).

    CAS  PubMed  Google Scholar 

  37. Durand, B. & Raff, M. A cell-intrinsic timer that operates during oligodendrocyte development. Bioessays 22, 64–71 (2000).

    Article  CAS  PubMed  Google Scholar 

  38. de Nooij, J. C., Letendre, M. A. & Hariharan, I. K. A cyclin-dependent kinase inhibitor, Dacapo, is necessary for timely exit from the cell cycle during Drosophila embryogenesis. Cell 87, 1237– 1247 (1996).

    Article  CAS  PubMed  Google Scholar 

  39. Lane, M. E. et al. Dacapo, a cyclin-dependent kinase inhibitor, stops cell proliferation during Drosophila development. Cell 87, 1225–1235 (1996).

    Article  CAS  PubMed  Google Scholar 

  40. Bromleigh, V. C. & Freedman, L. P. p21 is a transcriptional target of HOXA10 in differentiating myelomonocytic cells. Genes Dev. 14, 2581–2586 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Sigrist, S. J. & Lehner, C. F. Drosophila fizzy-related down-regulates mitotic cyclins and is required for cell proliferation arrest and entry into endocycles. Cell 90, 671–681 (1997).

    Article  CAS  PubMed  Google Scholar 

  42. Stiffler, L. A., Ji, J. Y., Trautmann, S., Trusty, C. & Schubiger, G. Cyclin A and B functions in the early Drosophila embryo. Development 126, 5505–5513 (1999).

    CAS  PubMed  Google Scholar 

  43. Fogarty, P., Kalpin, R. F. & Sullivan, W. The Drosophila maternal-effect mutation grapes causes a metaphase arrest at nuclear cycle 13. Development 120, 2131–2142 ( 1994).

    CAS  PubMed  Google Scholar 

  44. Sibon, O. C., Stevenson, V. A. & Theurkauf, W. E. DNA-replication checkpoint control at the Drosophila midblastula transition. Nature 388, 93–97 (1997).

    Article  CAS  PubMed  Google Scholar 

  45. Brodsky, M. H., Sekelsky, J. J., Tsang, G., Hawley, R. S. & Rubin, G. M. mus304 encodes a novel DNA damage checkpoint protein required during Drosophila development. Genes Dev. 14, 666– 678 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Sibon, O. C., Laurencon, A., Hawley, R. & Theurkauf, W. E. The Drosophila ATM homologue Mei-41 has an essential checkpoint function at the midblastula transition. Curr. Biol. 9, 302–312 (1999).

    Article  CAS  PubMed  Google Scholar 

  47. Royzman, I., Austin, R. J., Bosco, G., Bell, S. P. & Orr-Weaver, T. L. ORC localization in Drosophila follicle cells and the effects of mutations in dE2F and dDP. Genes Dev. 13, 827–840 ( 1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Datar, S. A., Jacobs, H. W., de La Cruz, A. F., Lehner, C. F. & Edgar, B. A. The Drosophila cyclin D–cdk4 complex promotes cellular growth. EMBO J. 19, 4543–4554 ( 2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Meyer, C. A. et al. Drosophila cdk4 is required for normal growth and is dispensable for cell cycle progression. EMBO J. 19, 4533–4542 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sherr, C. J. G1 phase progression: cycling on cue. Cell 79, 551–555 (1994).

    Article  CAS  PubMed  Google Scholar 

  51. Sherr, C. J. & Roberts, J. M. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 13, 1501–1512 ( 1999).

    Article  CAS  PubMed  Google Scholar 

  52. Lin, S. C., Skapek, S. X. & Lee, E. Y. Genes in the RB pathway and their knockout in mice . Semin. Cancer Biol. 7, 279– 289 (1996).

    Article  CAS  PubMed  Google Scholar 

  53. Brown, E. J. & Baltimore, D. ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes Dev. 14, 397–402 ( 2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Liu, Q. et al. Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Genes Dev. 14 , 1448–1459 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. de Klein, A. et al. Targeted disruption of the cell-cycle checkpoint gene ATR leads to early embryonic lethality in mice. Curr. Biol. 10, 479–482 (2000).

    Article  CAS  PubMed  Google Scholar 

  56. Takai, H. et al. Aberrant cell cycle checkpoint function and early embryonic death in Chk1(−/−) mice. Genes Dev. 14, 1439–1447 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank R. Feldman, P. O'Farrell, T. Shermoen, S. Prochnik, S. Jespersen, L. Hwang and S. van den Heuvel for critical comments on the manuscript. We acknowledge financial support from HHMI (to S. J. V.) and ACS (to T. T. S.).

Author information

Authors and Affiliations

  1. Department of Biochemistry and Biophysics, University of California at San Francisco, California, 94143-0448 , USA

    Smruti J Vidwans

  2. Department of Molecular, Cellular and Developmental Biology, University of Colorado at Boulder, Colorado, 80309-0347, USA

    Tin Tin Su

Authors
  1. Smruti J Vidwans
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tin Tin Su
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vidwans, S., Su, T. Cycling through development in Drosophila and other metazoa. Nat Cell Biol 3, E35–E39 (2001). https://doi.org/10.1038/35050681

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/35050681

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing