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Cells compete for Decapentaplegic survival factor to prevent apoptosis in Drosophila wing development

Nature volume 416, pages 755–759 (2002)Cite this article

Abstract

During the growth of Drosophila imaginal discs a process called ‘cell competition’1 eliminates slow-proliferating but otherwise viable cells. We report here that cell competition requires the function of the brinker (brk) gene, whose expression is normally repressed by Decapentaplegic (Dpp) signalling2,3,4 but is upregulated in slow-growing Minute/+ cells. Excess brk expression activates the c-Jun amino-terminal kinase pathway, which in turn triggers apoptosis in these cells. We propose that slow-proliferating cells upregulate Brk levels owing to a disadvantage in competing for, or in transducing, the Dpp survival signal. This sequence of events might represent a general mechanism by which weaker cells are eliminated from a growing population, and might serve as a method of controlling cell number and optimizing tissue fitness and hence organ function.

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Figure 1: Mitotic recombination method for inducing marked clones with one or three doses of the M(2)60E gene (see Methods for further details).
Figure 2: Cell competition is mediated by JNK-dependent apoptosis.
Figure 3: Cell competition is associated with, and caused by, brk upregulation.
Figure 4: Brk induces JNK-dependent apoptosis.
Figure 5: Decrease in Dpp signalling during cell competition and during endocytic blockage.

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References

  1. Morata, G. & Ripoll, P. Minutes: mutants of Drosophila autonomously affecting cell division rate. Dev. Biol. 42, 211–221 (1975).

    Article  CAS  Google Scholar 

  2. Minami, M., Kinoshita, N., Kamoshida, Y., Tanimoto, H. & Tabata, T. brinker is a target of Dpp in Drosophila that negatively regulates Dpp-dependent genes. Nature 398, 242–246 (1999).

    Article  ADS  CAS  Google Scholar 

  3. Jazwinska, A., Kirov, N., Wieschaus, E., Roth, S. & Rushlow, C. The Drosophila gene brinker reveals a novel mechanism of Dpp target gene regulation. Cell 96, 563–573 (1999).

    Article  CAS  Google Scholar 

  4. Campbell, G. & Tomlinson, A. Transducing the Dpp morphogen gradient in the wing of Drosophila: regulation of Dpp targets by brinker. Cell 96, 553–562 (1999).

    Article  CAS  Google Scholar 

  5. Conlon, I. & Raff, M. Size control in animal development. Cell 96, 235–244 (1999).

    Article  CAS  Google Scholar 

  6. Lawrence, P. A. Morphogens: how big is the big picture? Nature Cell Biol. 3, 151–154 (2001).

    Article  Google Scholar 

  7. Lambertsson, A. The Minute genes in Drosophila and their molecular functions. Adv. Genet. 38, 69–134 (1998).

    Article  CAS  Google Scholar 

  8. Simpson, P. Parameters of cell competition in the compartments of the wing of Drosophila. Dev. Biol. 69, 182–193 (1979).

    Article  CAS  Google Scholar 

  9. Simpson, P. & Morata, G. Differential mitotic rates and pattern of growth in compartments in the Drosophila wing. Dev. Biol. 85, 299–308 (1981).

    Article  CAS  Google Scholar 

  10. Böhni, R. et al. Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4. Cell 97, 865–875 (1999).

    Article  Google Scholar 

  11. 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  Google Scholar 

  12. Prober, D. & Edgar, B. ras1 promotes cellular growth in the Drosophila wing. Cell 100, 435–446 (2000).

    Article  CAS  Google Scholar 

  13. 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  Google Scholar 

  14. Gavrieli, Y., Sherman, Y. & Ben-Sasson, S. A. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J. Cell Biol. 119, 493–501 (1992).

    Article  CAS  Google Scholar 

  15. Hay, B. A., Wolff, T. & Rubin, G. M. Expression of baculovirus p35 prevents cell death in Drosophila. Development 120, 2121–2129 (1994).

    CAS  PubMed  Google Scholar 

  16. Adachi-Yamada, T., Fujimura-Kamada, K., Nishida, Y. & Matsumoto, K. Distortion of proximodistal information causes JNK-dependent apoptosis in Drosophila wing. Nature 400, 166–169 (1999).

    Article  ADS  CAS  Google Scholar 

  17. Martin-Blanco, E. et al. puckered encodes a phosphatase that mediates a feedback loop regulating JNK activity during dorsal closure in Drosophila. Genes Dev. 12, 557–570 (1998).

    Article  CAS  Google Scholar 

  18. Glise, B., Bourbon, H. & Noselli, S. hemipterous encodes a novel Drosophila MAP kinase kinase, required for epithelial cell sheet movement. Cell 83, 451–461 (1995).

    Article  CAS  Google Scholar 

  19. Burke, R. & Basler, K. Dpp receptors are autonomously required for cell proliferation in the entire developing Drosophila wing. Development 122, 2261–2269 (1996).

    CAS  PubMed  Google Scholar 

  20. Zhang, H., Levine, M. & Ashe, H. L. Brinker is a sequence-specific transcriptional repressor in the Drosophila embryo. Genes Dev. 15, 261–266 (2001).

    Article  CAS  Google Scholar 

  21. Tanimoto, H., Itoh, S., ten Dijke, P. & Tabata, T. Hedgehog creates a gradient of DPP activity in Drosophila wing imaginal discs. Mol. Cell 5, 59–71 (2000).

    Article  CAS  Google Scholar 

  22. Tsukazaki, T., Chiang, T. A., Davidson, A. F., Attisano, L. & Wrana, J. L. SARA, a FYVE domain protein that recruits Smad2 to the TGF-β receptor. Cell 95, 779–791 (1998).

    Article  CAS  Google Scholar 

  23. Entchev, E. V., Schwabedissen, A. & Gonzalez-Gaitan, M. Gradient formation of the TGF-β homolog Dpp. Cell 103, 981–991 (2000).

    Article  CAS  Google Scholar 

  24. Struhl, G., Barbash, D. A. & Lawrence, P. A. Hedgehog acts by distinct gradient and signal relay mechanisms to organise cell type and cell polarity in the Drosophila abdomen. Development 124, 2155–2165 (1999).

    Google Scholar 

  25. Raff, M. C. Social controls on cell survival and cell death. Nature 356, 397–400 (1992).

    Article  ADS  CAS  Google Scholar 

  26. Adams, M. D. et al. The genome sequence of Drosophila melanogaster. Science 287, 2185–2195 (2000).

    Article  Google Scholar 

  27. Milán, M., Campuzano, S. & García-Bellido, A. Developmental parameters of cell death in the wing disc of Drosophila. Proc. Natl Acad. Sci. USA 94, 5691–5696 (1997).

    Article  ADS  Google Scholar 

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Acknowledgements

We thank T. Adachi-Yamada, G. Campbell, M. Calleja, A. Cantarero, S. González-Crespo, M. Gonzalez-Gaitan, E. Hafen, A. Jazwinska, E. Martin-Blanco, B. Müller, E. Sánchez-Herrero, M. Suzanne and P. ten Dijke for fly stocks and antibodies; R. González for technical assistance; S. Campuzano for help with the TUNEL technique; C. Sánchez for help with confocal microscopy; and M. Calleja, O. Gerlitz, E. Hafen, G. Hausmann, P. Lawrence, F. Martin, B. Müller, D. Nellen, E. Sánchez-Herrero, H. Stocker and members of our laboratories for discussions. E.M. was supported by a postdoctoral fellowship from the Comunidad Autónoma de Madrid and the Swiss National Science Foundation.

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  1. Institut für Molekularbiologie, Universität Zürich, Winterthurerstrasse 190, Zürich, 8057, Switzerland

    Eduardo Moreno & Konrad Basler

  2. Centro de Biologia Molecular CSIC-UAM, Cantoblanco, 28049, Madrid, Spain

    Eduardo Moreno & Ginés Morata

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  1. Eduardo Moreno
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Correspondence to Konrad Basler or Ginés Morata.

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Moreno, E., Basler, K. & Morata, G. Cells compete for Decapentaplegic survival factor to prevent apoptosis in Drosophila wing development. Nature 416, 755–759 (2002). https://doi.org/10.1038/416755a

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