Abstract
We carried out gain-of-function mutagenesis screening and identified a mutant in which GAL4 induction led to both hyperplasia and apoptosis. The gene involved was identified as stonewall (stwl), a myb-related gene involved in germ cell proliferation and differentiation during oogenesis. As observed with dmyb, the ectopic expression of stwlUY823 inhibited endoreplication in salivary glands. We also found that stwlUY823 overexpression, like overexpression of the wild-type gene, activated G1/S transition and apoptosis. The apoptosis triggered by stwlUY823 expression is correlated to induction of the proapoptotic gene reaper. Finally, the death of flies induced by ectopic stwlUY823 expression is efficiently prevented in vivo by triggering cell death in stwlUY823-expressing cells. Our results suggest that stwlUY823 kills flies by causing inappropriate cell cycle entry, and that triggering the death of these overproliferating cells or slowing their proliferation restores viability.
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Abbreviations
- AO:
-
acridine orange
- Brat gene:
-
brain tumor gene
- BrdU:
-
bromodeoxyuridine
- CDS:
-
coding DNA sequence
- CyO:
-
curly of Oster
- da :
-
daughterless
- Dpp :
-
decapentaplegic
- en :
-
engrailed
- fkh :
-
fork head
- GFP:
-
green fluorescent protein
- gmr:
-
glass-mediated response
- GUS:
-
gmr UAS
- hid :
-
head involution defective
- Hs:
-
heat shock
- hsp70:
-
heat-shock protein 70
- ORF:
-
open reading frame
- PBS:
-
phosphate-buffered saline
- PCD:
-
programmed cell death
- rpr :
-
reaper
- Sev :
-
sevenless
- stwl :
-
stonewall
- UAS:
-
upstream activating sequences
- vg :
-
vestigial
- ywc:
-
yellow white C
- ZNC:
-
zone of nonproliferating cells
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Acknowledgements
We thank E Blanchardon for drawing our attention to the UY823 line, F Leulier for providing us with the UAS-dreddδ line, D McKearin, who generously provided us with the stwlΔ95 and the hsp70-stwl mutant strains, the P{w+, minigene stwl} line and the vector containing the stwl cDNA, S Beckendorf, who provided us with the fkh-GAL4 strain, and the Bloomington Drosophila Stock Center for fly stocks. The GS3129 line was a gift from T Aigaki. We also thank I Séminet for performing some of the experiments described in this paper, P Gandille for technical assistance with confocal microscopy, S Gaumer and C Stenbak for critical reading of the manuscript, and J Sappa (from A Edelman & Associates) for English rereading. This work was supported in part by grants from the Association pour la Recherche Contre le Cancer (#3367) and the Ligue Nationale Contre le Cancer. Sylvain Brun held successive fellowships from the Ministère de l’Education Nationale, de l’Enseignement Supérieur et de la Recherche, the Fondation pour la Recherche Médicale and the Association pour la Recherche contre le Cancer.
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Brun, S., Rincheval-Arnold, A., Colin, J. et al. The myb-related gene stonewall induces both hyperplasia and cell death in Drosophila: rescue of fly lethality by coexpression of apoptosis inducers. Cell Death Differ 13, 1752–1762 (2006). https://doi.org/10.1038/sj.cdd.4401861
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DOI: https://doi.org/10.1038/sj.cdd.4401861
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