TY - JOUR
T1 - A retrograde neuronal survival response
T2 - Target-derived neurotrophins regulate MEF2D and bcl-w
AU - Pazyra-Murphy, Maria F.
AU - Hans, Aymeric
AU - Courchesne, Stephanie L.
AU - Karch, Christoph
AU - Cosker, Katharina E.
AU - Heerssen, Heather M.
AU - Watson, Fiona L.
AU - Kim, Taekyung
AU - Greenberg, Michael E.
AU - Segal, Rosalind A.
PY - 2009/5/20
Y1 - 2009/5/20
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=66249114341&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.0233-09.2009
DO - 10.1523/JNEUROSCI.0233-09.2009
M3 - Article
C2 - 19458239
AN - SCOPUS:66249114341
SN - 0270-6474
VL - 29
SP - 6700
EP - 6709
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 20
ER -