Abstract
Most of the 131 cells that die during the development of a Caenorhabditis elegans hermaphrodite do so ∼30 min after being generated. Furthermore, in these cells, the pro-caspase proCED-3 is inherited from progenitors and the transcriptional upregulation of the BH3-only gene egl-1 is thought to be sufficient for apoptosis induction. In contrast, the four CEM neurons, which die in hermaphrodites, but not males, die ∼150 min after being generated. We found that in the CEMs, the transcriptional activation of both the egl-1 and ced-3 gene is necessary for apoptosis induction. In addition, we show that the Bar homeodomain transcription factor CEH-30 represses egl-1 and ced-3 transcription in the CEMs, thereby permitting their survival. Furthermore, we identified three genes, unc-86, lrs-1, and unc-132, which encode a POU homeodomain transcription factor, a leucyl-tRNA synthetase, and a novel protein with limited sequence similarity to the mammalian proto-oncoprotein and kinase PIM-1, respectively, that promote the expression of the ceh-30 gene in the CEMs. On the basis of these results, we propose that egl-1 and ced-3 transcription are coregulated in the CEMs to compensate for limiting proCED-3 levels, which most probably are a result of proCED-3 turn over. Similar coregulatory mechanisms for BH3-only proteins and pro-caspases may function in higher organisms to allow efficient apoptosis induction. Finally, we present evidence that the timing of the death of the CEMs is controlled by TRA-1 Gli, the terminal global regulator of somatic sexual fate in C. elegans.
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Abbreviations
- CED:
-
cell-death abnormal
- EGL:
-
egg-laying abnormal
- CEM:
-
cephalic companion neurons
- UNC:
-
uncoordinated
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Acknowledgements
We thank E. Lambie and S. Rolland for comments on the manuscript; H. Schwartz, M. Saito, J. Dunlap, and members of the Conradt laboratory for discussions; D. Mayka and C. Huber for excellent technical support; E. Lambie for use of the micro-injection set-up; H. Schwartz and B. Horvitz for array nEx1171 (Pceh−30ceh-30::gfp); S. Shaham for array nsEx37 (Pcfi−1gfp) and a ced-3 reporter; N. Pujol for array bgEx21 (Punc−53gfp); V. Maricq for array akEx32 (Pglr−4glr-4::gfp); M. Barr for array syEx301 (Plov−1gfp) and plasmid Ppkd−2gfp; the Sanger Centre (Hinxton, UK) for cosmids; and the C. elegans Genetics Center (CGC, supported by the NIH National Center for Research Resources) for strains. This work was supported by funding from the Max Planck Society, Howard Hughes Medical Institute Award 76200-560801 to Dartmouth Medical School under the Biomedical Research Support Program for Medical Schools, and National Institute of Health grant R01-GM069950.
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Nehme, R., Grote, P., Tomasi, T. et al. Transcriptional upregulation of both egl-1 BH3-only and ced-3 caspase is required for the death of the male-specific CEM neurons. Cell Death Differ 17, 1266–1276 (2010). https://doi.org/10.1038/cdd.2010.3
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DOI: https://doi.org/10.1038/cdd.2010.3
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