Embryonic neuronal death due to neurotrophin and neurotransmitter deprivation occurs independent of Apaf-1

N. Honarpour, K. Tabuchi, J. M. Stark, Robert E Hammer, T. C. Südhof, L. F. Parada, X. Wang, James A Richardson, Joachim Herz

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Apoptotic protease-activating factor-1 (Apaf-1), dATP, and procaspase-9 form a multimeric complex that triggers programmed cell death through the activation of caspases upon release of cytochrome c from the mitochondria into the cytosol. Although cell death pathways exist that can bypass the requirement for cytochrome c release and caspase activation, several gene knockout studies have shown that the cytochrome c-mediated apoptotic pathway is critical for neural development. Specifically, the number of neuronal progenitor cells is abnormally increased in Apaf-1-, caspase-9-, caspase-3-deficient mice. However, the role of the cytochrome c cell death pathway for apoptosis of postmitotic, differentiated neurons in the developing brain has not been investigated in vivo. In this study we investigated embryonic neuronal cell death caused by trophic factor deprivation or lack of neurotransmitter release by analyzing Apaf-1/tyrosine kinase receptor A (TrkA) and Apaf-1/Munc-18 double mutant mice. Histological analysis of the double mutants' brains (including cell counting and terminal (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) staining) reveals that neuronal cell death caused by these stimuli can proceed independent of Apaf-1. We propose that a switch between apoptotic programs (and their respective proteins) characterizes the transition of a neuronal precursor cell from the progenitor pool to the postmitotic population of differentiated neurons.

Original languageEnglish (US)
Pages (from-to)263-274
Number of pages12
JournalNeuroscience
Volume106
Issue number2
DOIs
StatePublished - Sep 6 2001

Keywords

  • Apoptosis
  • Caspase
  • Cell death
  • Cytochrome c
  • Mouse
  • Neuron

ASJC Scopus subject areas

  • Neuroscience(all)

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