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

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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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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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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