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A Retrograde Neuronal Survival Response: Target-Derived Neurotrophins Regulate MEF2D and bcl-w

Authors :
Heather M. Heerssen
Christoph Karch
Fiona L. Watson
Michael E. Greenberg
Tae Kyung Kim
Rosalind A. Segal
Stephanie L. Courchesne
Maria F. Pazyra-Murphy
Aymeric Hans
Katharina E. Cosker
Source :
The Journal of Neuroscience. 29:6700-6709
Publication Year :
2009
Publisher :
Society for Neuroscience, 2009.

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-apoptoticbcl-2family member,bcl-w. Expression ofmef2dandbcl-wis 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 thatmef2dandbcl-ware 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.

Details

ISSN :
15292401 and 02706474
Volume :
29
Database :
OpenAIRE
Journal :
The Journal of Neuroscience
Accession number :
edsair.doi.dedup.....322f57e41d65c4e13472f56172e46630