Regulation of armadillo by a Drosophila APC inhibits neuronal apoptosis during retinal development

Cell. 1998 Jun 26;93(7):1171-82. doi: 10.1016/s0092-8674(00)81461-0.

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