TY - JOUR
T1 - A Hierarchical NGF Signaling Cascade Controls Ret-Dependent and Ret-Independent Events during Development of Nonpeptidergic DRG Neurons
AU - Luo, Wenqin
AU - Wickramasinghe, S. Rasika
AU - Savitt, Joseph M.
AU - Griffin, John W.
AU - Dawson, Ted M.
AU - Ginty, David D.
N1 - Funding Information:
We thank Drs. Alex Kolodkin, Valina L. Dawson, and Xinzhong Dong and members of the Ginty laboratory for helpful discussions and comments on this manuscript. We thank Dr. Story Landis for valuable comments and suggestions. We thank Ting Guo, Kenji Mandai, Hasan Janbieh, and Michelle Polley for reagents, technical support, and valuable comments, Narendrakumar Ramanan for help with targeting strategy design, Dori Reimert for homologous recombination and ES cell work, and Chip Hawkins and the Johns Hopkins Transgenic Facility for blastocyst injections and advice with ES cells. This work was supported by National Institutes of Health Grant NS34814 (D.D.G.), K08 NS052624 (J.M.S.), NS38377 (T.M.D.), the George C. Cotzias Fellowship, the American Parkinson Disease Association (J.M.S.), the Michael J. Fox Foundation (T.M.D. and J.M.S.), and the Medical Scientist Training Program Grant 5T32GMO7309 (S.R.W.). T.M.D. is the Leonard and Madlyn Abramson Professor in Neurodegenerative Disease. D.D.G. is an investigator of the Howard Hughes Medical Institute.
PY - 2007/6/7
Y1 - 2007/6/7
N2 - NGF controls survival, differentiation, and target innervation of both peptidergic and nonpeptidergic DRG sensory neurons. The common receptor for GDNF family ligands, Ret, is highly expressed in nonpeptidergic neurons, but its function during development of these neurons is unclear. Here, we show that expression of Ret and its coreceptors GFRα1 and GFRα2 is dependent on NGF. GFR/Ret signaling, in turn, autoregulates expression of both GFRα1 and GFRα2 and promotes expression of TrpA1, MrgA1, MrgA3, and MrgB4, acquisition of normal neuronal size, axonal innervation of the epidermis, and postnatal extinction of the NGF receptor TrkA. Moreover, NGF controls expression of several other genes characteristic of nonpeptidergic neurons, such as TrpC3, TrpM8, MrgD, and the transcription factor Runx1, via a Ret-independent signaling pathway. These findings support a model in which NGF controls maturation of nonpeptidergic DRG neurons through a combination of GFR/Ret-dependent and -independent signaling pathways.
AB - NGF controls survival, differentiation, and target innervation of both peptidergic and nonpeptidergic DRG sensory neurons. The common receptor for GDNF family ligands, Ret, is highly expressed in nonpeptidergic neurons, but its function during development of these neurons is unclear. Here, we show that expression of Ret and its coreceptors GFRα1 and GFRα2 is dependent on NGF. GFR/Ret signaling, in turn, autoregulates expression of both GFRα1 and GFRα2 and promotes expression of TrpA1, MrgA1, MrgA3, and MrgB4, acquisition of normal neuronal size, axonal innervation of the epidermis, and postnatal extinction of the NGF receptor TrkA. Moreover, NGF controls expression of several other genes characteristic of nonpeptidergic neurons, such as TrpC3, TrpM8, MrgD, and the transcription factor Runx1, via a Ret-independent signaling pathway. These findings support a model in which NGF controls maturation of nonpeptidergic DRG neurons through a combination of GFR/Ret-dependent and -independent signaling pathways.
KW - CELLBIO
KW - DEVBIO
KW - SIGNALING
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U2 - 10.1016/j.neuron.2007.04.027
DO - 10.1016/j.neuron.2007.04.027
M3 - Article
C2 - 17553423
AN - SCOPUS:34249743706
SN - 0896-6273
VL - 54
SP - 739
EP - 754
JO - Neuron
JF - Neuron
IS - 5
ER -