Characterization of a neurotrophin signaling mechanism that mediates neuron survival in a temporally specific pattern

Aryaman Shalizi, Maria Lehtinen, Brice Gaudillière, Nicole Donovan, Jiahuai Han, Yoshiyuki Konishi, Azad Bonni

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

The temporally specific nature of neurotrophic factor-induced responses is a general feature of mammalian nervous system development, the mechanisms of which remain to be elucidated. We characterized a mechanism underlying the temporal specificity by which BDNF selectively promotes the survival of newly generated, but not mature, granule neurons of the mammalian cerebellum. We found that BDNF specifically induces the extracellular signal-regulated kinase 5 (ERK5)-myocyte enhancer factor (MEF2) signaling pathway in newly generated granule neurons and thereby induces transcription of neurotrophin-3 (NT-3), a novel gene target of MEF2. Inhibition of endogenous ERK5, MEF2, or NT-3 in neurons by several approaches including disruption of the NT-3 gene in mice revealed a requirement for the ERK5-MEF2-NT-3 signaling pathway in BDNF-induced survival of newly generated granule neurons. These findings define a novel mechanism that underlies the antiapoptotic effect of neurotrophins in a temporally defined pattern in the developing mammalian brain.

Original languageEnglish
Pages (from-to)7326-7336
Number of pages11
JournalJournal of Neuroscience
Volume23
Issue number19
StatePublished - Aug 13 2003

Keywords

  • Apoptosis
  • BDNF
  • CREB
  • ERK5
  • MEF2
  • NT-3
  • Neuron
  • Survival
  • Transcription

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    Shalizi, A., Lehtinen, M., Gaudillière, B., Donovan, N., Han, J., Konishi, Y., & Bonni, A. (2003). Characterization of a neurotrophin signaling mechanism that mediates neuron survival in a temporally specific pattern. Journal of Neuroscience, 23(19), 7326-7336.