Serum response factor mediates NGF-dependent target innervation by embryonic DRG sensory neurons.
Serum response factor (SRF) is a prototypic transcription factor that mediates stimulus-dependent gene expression. Here, we show that SRF mediates NGF signaling, axonal growth, branching, and target innervation by embryonic DRG sensory neurons. Conditional deletion of the murine SRF gene in DRGs results in no deficits in neuronal viability or differentiation but causes defects in extension and arborization of peripheral axonal projections in the target field in vivo, similar to the target innervation defects observed in mice lacking NGF. Moreover, SRF is both necessary and sufficient for NGF-dependent axonal outgrowth in vitro, and NGF regulates SRF-dependent gene expression and axonal outgrowth through activation of both MEK/ERK and MAL signaling pathways. These findings show that SRF is a major effector of both MEK/ERK and MAL signaling by NGF and that SRF is a key mediator of NGF-dependent target innervation by embryonic sensory neurons.
Wickramasinghe
S Rasika
SR
The Solomon H. Snyder Department of Neuroscience, The Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, PCTB 1015, Baltimore, MD 21205, USA.
Alvania
Rebecca S
RS
Ramanan
Narendrakumar
N
Wood
John N
JN
Mandai
Kenji
K
Ginty
David D
DD
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D008156:Luciferases / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000502:physiology; D020932:Nerve Growth Factor / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000172:deficiency
D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C469338:Sef protein, mouse; D051028:bcl-2-Associated X Protein; D020932:Nerve Growth Factor; D008156:Luciferases