[HTML][HTML] A hierarchical NGF signaling cascade controls Ret-dependent and Ret-independent events during development of nonpeptidergic DRG neurons

W Luo, SR Wickramasinghe, JM Savitt, JW Griffin… - Neuron, 2007 - cell.com
W Luo, SR Wickramasinghe, JM Savitt, JW Griffin, TM Dawson, DD Ginty
Neuron, 2007cell.com
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 …
Summary
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 TrpC3TrpM8, 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.
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