The myb-related gene stonewall induces both hyperplasia and cell death in Drosophila: rescue of fly lethality by coexpression of apoptosis inducers.
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 stwl(UY823) inhibited endoreplication in salivary glands. We also found that stwl(UY823) overexpression, like overexpression of the wild-type gene, activated G1/S transition and apoptosis. The apoptosis triggered by stwl(UY823) expression is correlated to induction of the proapoptotic gene reaper. Finally, the death of flies induced by ectopic stwl(UY823) expression is efficiently prevented in vivo by triggering cell death in stwl(UY823)-expressing cells. Our results suggest that stwl(UY823) kills flies by causing inappropriate cell cycle entry, and that triggering the death of these overproliferating cells or slowing their proliferation restores viability.
Brun
S
S
Laboratoire de Génétique et Biologie Cellulaire, CNRS MR 8159, Université de Versailles-St. Quentin en Yvelines, 45 avenue des Etats-Unis, F-78035 Versailles cedex, France.
Rincheval-Arnold
A
A
Colin
J
J
Risler
Y
Y
Mignotte
B
B
Guénal
I
I
D000483:Alleles; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D002453:Cell Cycle; D049109:Cell Proliferation; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004330:Drosophila / Q000166:cytology* / Q000235:genetics* / Q000254:growth & development; D029721:Drosophila Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D017344:Genes, Insect; D005804:Genes, Lethal; D005816:Genetic Complementation Test; D005822:Genetic Vectors; D006965:Hyperplasia; D008297:Male; D016296:Mutagenesis; D010641:Phenotype; D011679:Pupa / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D012469:Salivary Glands / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014921:Wings, Animal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D014157:Transcription Factors; C086973:rpr protein, Drosophila; C098675:stwl protein, Drosophila