Genes affecting cell competition in Drosophila.
Cell competition is a homeostatic mechanism that regulates the size attained by growing tissues. We performed an unbiased genetic screen for mutations that permit the survival of cells being competed due to haplo-insufficiency for RpL36. Mutations that protect RpL36 heterozygous clones include the tumor suppressors expanded, hippo, salvador, mats, and warts, which are members of the Warts pathway, the tumor suppressor fat, and a novel tumor-suppressor mutation. Other hyperplastic or neoplastic mutations did not rescue RpL36 heterozygous clones. Most mutations that rescue cell competition elevated Dpp-signaling activity, and the Dsmurf mutation that elevates Dpp signaling was also hyperplastic and rescued. Two nonlethal, nonhyperplastic mutations prevent the apoptosis of Minute heterozygous cells and suggest an apoptosis pathway for cell competition . In addition to rescuing RpL36 heterozygous cells, mutations in Warts pathway genes were supercompetitors that could eliminate wild-type cells nearby. The findings show that differences in Warts pathway activity can lead to competition and implicate the Warts pathway, certain other tumor suppressors, and novel cell death components in cell competition, in addition to the Dpp pathway implicated by previous studies. We suggest that cell competition might occur during tumor development in mammals.
Tyler
David M
DM
Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Li
Wei
W
Zhuo
Ning
N
Pellock
Brett
B
Baker
Nicholas E
NE
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics*; D017344:Genes, Insect; D016147:Genes, Tumor Suppressor; D005820:Genetic Testing; D018869:Heat-Shock Response / Q000235:genetics; D006965:Hyperplasia; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics; D009154:Mutation / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
D029721:Drosophila Proteins; D048031:JNK Mitogen-Activated Protein Kinases