Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adenomatous Polyposis Coli Protein
-
Animals
-
Apoptosis / physiology*
-
Armadillo Domain Proteins
-
Cytoskeletal Proteins / analysis
-
Cytoskeletal Proteins / physiology
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / physiology
-
Drosophila / embryology
-
Drosophila / genetics*
-
Drosophila Proteins*
-
Gene Expression Regulation, Developmental / physiology
-
Genes, APC / physiology*
-
Insect Proteins / analysis
-
Insect Proteins / genetics
-
Insect Proteins / physiology*
-
Mutation
-
Photoreceptor Cells, Invertebrate / cytology*
-
Proto-Oncogene Proteins / genetics
-
Proto-Oncogene Proteins / physiology
-
Repetitive Sequences, Nucleic Acid
-
Repressor Proteins*
-
Retina / embryology
-
Retina / growth & development
-
Retinal Degeneration / genetics
-
Signal Transduction
-
Trans-Activators*
-
Transcription Factors / genetics
-
Transcription Factors / physiology
-
Wnt1 Protein
-
beta Catenin
Substances
-
ARM protein, Drosophila
-
Adenomatous Polyposis Coli Protein
-
Armadillo Domain Proteins
-
Cytoskeletal Proteins
-
DNA-Binding Proteins
-
Drosophila Proteins
-
Insect Proteins
-
Proto-Oncogene Proteins
-
Repressor Proteins
-
Trans-Activators
-
Transcription Factors
-
Wnt1 Protein
-
beta Catenin
-
pan protein, Drosophila
-
wg protein, Drosophila
-
z protein, Drosophila