A retrograde neuronal survival response: Target-derived neurotrophins regulate MEF2D and bcl-w

Maria F. Pazyra-Murphy, Aymeric Hans, Stephanie L. Courchesne, Christoph Karch, Katharina E. Cosker, Heather M. Heerssen, Fiona L. Watson, Taekyung Kim, Michael E. Greenberg, Rosalind A. Segal

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Survival and maturation of dorsal root ganglia sensory neurons during development depend on target-derived neurotrophins. These target-derived signals must be transmitted across long distances to alter gene expression. Here, we address the possibility that long-range retrograde signals initiated by target-derived neurotrophins activate a specialized transcriptional program. The transcription factor MEF2D is expressed in sensory neurons; we show that expression of this factor is induced in response to target-derived neurotrophins that stimulate the distal axons. We demonstrate that MEF2D regulates expression of an anti-apoptotic bcl-2 family member, bcl-w. Expression of mef2d and bcl-w is stimulated in response to activation of a Trk-dependent ERK5/MEF2 pathway, and our data indicate that this pathway promotes sensory neuron survival. We find that mef2d and bcl-w are members of a larger set of retrograde response genes, which are preferentially induced by neurotrophin stimulation of distal axons. Thus, activation of an ERK5/MEF2D transcriptional program establishes and maintains the cellular constituents of functional sensory circuits.

Original languageEnglish (US)
Pages (from-to)6700-6709
Number of pages10
JournalJournal of Neuroscience
Volume29
Issue number20
DOIs
StatePublished - May 20 2009

ASJC Scopus subject areas

  • Neuroscience(all)

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    Pazyra-Murphy, M. F., Hans, A., Courchesne, S. L., Karch, C., Cosker, K. E., Heerssen, H. M., Watson, F. L., Kim, T., Greenberg, M. E., & Segal, R. A. (2009). A retrograde neuronal survival response: Target-derived neurotrophins regulate MEF2D and bcl-w. Journal of Neuroscience, 29(20), 6700-6709. https://doi.org/10.1523/JNEUROSCI.0233-09.2009