Regulation of armadillo by a Drosophila APC inhibits neuronal apoptosis during retinal development.
We find that inactivation of a Drosophila homolog of the tumor suppressor APC (D-APC) causes retinal neuronal degeneration and pigment cell hypertrophy, a phenotype remarkably similar to that found in humans with germline APC mutations. Retinal degeneration in the D-APC mutant results from apoptotic cell death, which accompanies a defect in neuronal differentiation. Reduction in the Drosophila beta-catenin, Armadillo (Arm), rescues the differentiation defect and prevents apoptosis in the D-APC mutant, while Arm overexpression mimics D-APC inactivation. A mutation in dTCF, the DNA-binding protein required in Arm-mediated signal transduction, can eliminate the cell death without rescuing the differentiation defect in D-APC mutants. Uncoupling of these two Arm-induced processes suggests a novel role for the Arm/dTCF complex in the activation of apoptosis.
Ahmed
Y
Y
Department of Molecular Biology, Princeton University, New Jersey 08544, USA.
Hayashi
S
S
Levine
A
A
Wieschaus
E
E
D025601:Adenomatous Polyposis Coli Protein; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051186:Armadillo Domain Proteins; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D017491:Genes, APC / Q000502:physiology*; D019476:Insect Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D012091:Repetitive Sequences, Nucleic Acid; D012097:Repressor Proteins; D012160:Retina / Q000196:embryology / Q000254:growth & development; D012162:Retinal Degeneration / Q000235:genetics; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D051155:Wnt1 Protein; D051176:beta Catenin
C495305:ARM protein, Drosophila; D025601:Adenomatous Polyposis Coli Protein; D051186:Armadillo Domain Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051155:Wnt1 Protein; D051176:beta Catenin; C115159:pan protein, Drosophila; C074622:wg protein, Drosophila; C060849:z protein, Drosophila