Distortion of proximodistal information causes JNK-dependent apoptosis in Drosophila wing

Nature. 1999 Jul 8;400(6740):166-9. doi: 10.1038/22112.


Distinct and evolutionarily conserved signal-transduction cascades mediate the survival or death of cells during development. The c-Jun amino-terminal kinases (JNKs) of the mitogen-activated protein kinase superfamily are involved in apoptotic signalling in various cultured cells. However, the role of the JNK pathway in development is less well understood. In Drosophila, Decapentaplegic (Dpp; a homologue of transforming growth factor-beta) and Wingless (Wg; a Wnt homologue) proteins are secretory morphogens that act cooperatively to induce formation of the proximodistal axis of appendages. Here we show that either decreased Dpp signalling in the distal wing cells or increased Dpp signalling in the proximal wing cells causes apoptosis. Inappropriate levels of Dpp signalling lead to aberrant morphogenesis in the respective wing zones, and these apoptotic zones are also determined by the strength of the Wg signal. Our results indicate that distortion of the positional information determined by Dpp and Wg signalling gradients leads to activation of the JNK apoptotic pathway, and the consequent induction of cell death thereby maintains normal morphogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridine Orange
  • Animals
  • Animals, Genetically Modified
  • Apoptosis*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Down-Regulation
  • Drosophila / embryology
  • Drosophila Proteins*
  • Enzyme Activation
  • Insect Proteins / metabolism*
  • JNK Mitogen-Activated Protein Kinases*
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases*
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Phosphoprotein Phosphatases / metabolism
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Signal Transduction
  • T-Box Domain Proteins*
  • Up-Regulation
  • Wings, Animal / cytology
  • Wings, Animal / embryology
  • Wnt1 Protein


  • DNA-Binding Proteins
  • Drosophila Proteins
  • Insect Proteins
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins
  • Receptors, Cell Surface
  • T-Box Domain Proteins
  • Wnt1 Protein
  • dpp protein, Drosophila
  • wg protein, Drosophila
  • bi protein, Drosophila
  • Protein Kinases
  • tkv protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases
  • puc protein, Drosophila
  • Phosphoprotein Phosphatases
  • Acridine Orange