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PMID: 19458239 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 29 ·No. 20 ·2009-05-20 ·Pages 6700-9

Pazyra-Murphy MF, Hans A, Courchesne SL, Karch C, Cosker KE, Heerssen HM, Watson FL, Kim T, Greenberg ME, Segal RA

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.

MeSH Terms
Animals Cell Survival/drug effects,physiology Cells, Cultured Chlorocebus aethiops Embryo, Mammalian Enzyme Inhibitors/pharmacology Ganglia, Spinal/cytology Gene Expression Regulation/drug effects,physiology Green Fluorescent Proteins/genetics In Situ Nick-End Labeling/methods Mitogen-Activated Protein Kinase 7/metabolism Nerve Growth Factors/pharmacology Nerve Tissue Proteins/genetics,metabolism Protein Tyrosine Phosphatases, Non-Receptor/genetics,metabolism Proto-Oncogene Proteins c-bcl-2/genetics,metabolism RNA Interference/physiology RNA, Messenger/metabolism Rats Sensory Receptor Cells/drug effects,physiology Signal Transduction/drug effects,genetics Transfection/methods
Chemicals
Enzyme Inhibitors Nerve Growth Factors Nerve Tissue Proteins Proto-Oncogene Proteins c-bcl-2 RNA, Messenger Green Fluorescent Proteins Mitogen-Activated Protein Kinase 7 PTPN9 protein, human Protein Tyrosine Phosphatases, Non-Receptor
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Pazyra-Murphy Maria F
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Hans Aymeric
Courchesne Stephanie L
Karch Christoph
Cosker Katharina E
Heerssen Heather M
Watson Fiona L
Kim Taekyung
Greenberg Michael E
Segal Rosalind A
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.0233-09.2009
Published
2009-05-20
Pages
6700-9
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC2709981
Subset
IM
Grants
NINDS NIH HHS · R01 NS050674 · United States
NINDS NIH HHS · R01 NS050674-04 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.0233-09.2009 PMC Full Text View journal details
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