Regulation of cell number by MAPK-dependent control of apoptosis: a mechanism for trophic survival signaling

Dev Cell. 2002 Feb;2(2):159-70. doi: 10.1016/s1534-5807(02)00116-8.

Abstract

Trophic mechanisms in which neighboring cells mutually control their survival by secreting extracellular factors play an important role in determining cell number. However, how trophic signaling suppresses cell death is still poorly understood. We now show that the survival of a subset of midline glia cells in Drosophila depends upon direct suppression of the proapoptotic protein HID via the EGF receptor/RAS/MAPK pathway. The TGFalpha-like ligand SPITZ is activated in the neurons, and glial cells compete for limited amounts of secreted SPITZ to survive. In midline glia that fail to activate the EGFR pathway, HID induces apoptosis by blocking a caspase inhibitor, Diap1. Therefore, a direct pathway linking a specific extracellular survival factor with a caspase-based death program has been established.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Caspase Inhibitors
  • Caspases / metabolism
  • Cell Count
  • Cell Survival / drug effects
  • Drosophila / cytology*
  • Drosophila / drug effects
  • Drosophila / embryology*
  • Drosophila / metabolism
  • Drosophila Proteins / antagonists & inhibitors
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / enzymology
  • Embryo, Nonmammalian / metabolism
  • Enzyme Activation
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors / metabolism
  • Inhibitor of Apoptosis Proteins
  • Insect Proteins / genetics
  • Insect Proteins / metabolism
  • MAP Kinase Signaling System* / drug effects
  • Membrane Proteins / metabolism
  • Mitogen-Activated Protein Kinases / metabolism*
  • Models, Biological
  • Neuroglia / cytology*
  • Neuroglia / drug effects
  • Neuroglia / enzymology
  • Neuroglia / metabolism*
  • Neurons / metabolism
  • Neuropeptides / antagonists & inhibitors
  • Neuropeptides / metabolism
  • Phosphorylation
  • ras Proteins / metabolism

Substances

  • Caspase Inhibitors
  • DIAP1 protein, Drosophila
  • Drosophila Proteins
  • HID protein, Drosophila
  • Inhibitor of Apoptosis Proteins
  • Insect Proteins
  • Membrane Proteins
  • Neuropeptides
  • spi protein, Drosophila
  • Epidermal Growth Factor
  • ErbB Receptors
  • Mitogen-Activated Protein Kinases
  • Caspases
  • ras Proteins