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首页> 外文期刊>Neuron >A hierarchical NGF signaling cascade controls Ret-dependent and Ret-independent events during development of nonpeptidergic DRG neurons.
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A hierarchical NGF signaling cascade controls Ret-dependent and Ret-independent events during development of nonpeptidergic DRG neurons.

机译：在非肽能DRG神经元发育过程中，分层NGF信号级联控制Ret依赖性和Ret非依赖性事件。

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摘要

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 GFRalpha1 and GFRalpha2 is dependent on NGF. GFR/Ret signaling, in turn, autoregulates expression of both GFRalpha1 and GFRalpha2 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.
机译：NGF控制肽能和非肽能DRG感觉神经元的存活，分化和靶标神经支配。 GDNF家族配体的常见受体Ret在非肽能神经元中高度表达，但在这些神经元发育过程中的功能尚不清楚。在这里，我们表明Ret及其共受体GFRalpha1和GFRalpha2的表达依赖于NGF。 GFR / Ret信号转而自动调节GFRalpha1和GFRalpha2的表达并促进TrpA1，MrgA1，MrgA3和MrgB4的表达，获得正常的神经元大小，表皮的轴突神经支配以及NGF受体TrkA的产后灭绝。此外，NGF通过独立于Ret的信号通路控制非肽能神经元的其他几个基因的表达，例如TrpC3，TrpM8，MrgD和转录因子Runx1。这些发现支持了一种模型，其中NGF通过GFR / Ret依赖性和非依赖性信号通路的组合来控制非肽能DRG神经元的成熟。

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