c-Maf Is Required for the Development of Dorsal Horn Laminae III/IV Neurons and Mechanoreceptive DRG Axon Projections
c-Maf Is Required for the Development of Dorsal Horn Laminae III/IV Neurons and Mechanoreceptive DRG Axon Projections
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DOI：
10.1523/jneurosci.6239-11.2012
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发表时间：
2012-04-18
影响因子：
5.3
通讯作者：
Cheng, Leping
中科院分区：
文献类型：
--
作者：
Hu, Jia;Huang, Tianwen;Cheng, Leping
动物感知和响应各种外部刺激需要外周感觉神经元与其中心目标之间建立适当的连接。背根神经节（Dorsal root ganglion， DRG）神经元通过轴突投射向脊髓背角不同的椎板传递不同形式的感觉信号。在这项研究中，我们发现c-Maf主要在III/IV层的中间神经元中表达，这些神经元主要接受机械感受性DRG神经元的输入。在DRG中，c-Maf（+）神经元也共同表达神经丝-200，这是传递无害信息的中、大直径髓鞘传入事件的标记物。此外，缺乏c-Maf的小鼠胚胎显示背角III/IV层神经元发育异常，这些神经元的几个标记基因表达显著减少，包括转录因子MafA和Rora， GABA(A)受体亚基α 5和神经肽胆囊收缩素。此外，在TrkA、TrkB、TrkC和MafA/GFR α 2/Ret表达的四个主要DRG神经元亚群中，c-Maf是MafA (+)/Ret (+)/GFR α 2（+）低阈值机械受体（ltm）正确分化所必需的。最后，我们发现在c-Maf缺失小鼠中，机械感受性DRG神经元的中枢和外周投射受到损害。综上所述，我们的研究结果表明，c-Maf是DRG中MafA (+)/Ret (+)/GFR α 2 (+) ltm的正常发育所必需的，它们在背角和太平洋小体中的传入投射，以及脊髓III/IV层的神经元。
Establishment of proper connectivity between peripheral sensory neurons and their central targets is required for an animal to sense and respond to various external stimuli. Dorsal root ganglion(DRG) neurons convey sensory signals of different modalities via their axon projections to distinct laminae in the dorsal horn of the spinal cord. In this study, we found that c-Maf was expressed predominantly in the interneurons of laminae III/IV, which primarily receive inputs from mechanoreceptive DRG neurons. In the DRG, c-Maf(+) neurons also coexpressed neurofilament-200, a marker for the medium-and large-diameter myelinated afferents that transmit non-noxious information. Furthermore, mouse embryos deficient in c-Maf displayed abnormal development of dorsal horn laminae III/IV neurons, as revealed by the marked reduction in the expression of several marker genes for these neurons, including those for transcription factors MafA and Rora, GABA(A) receptor subunit alpha 5, and neuropeptide cholecystokinin. In addition, among the four major subpopulations of DRG neurons marked by expression of TrkA, TrkB, TrkC, and MafA/GFR alpha 2/Ret, c-Maf was required selectively for the proper differentiation of MafA (+)/Ret (+)/GFR alpha 2 (+) low-threshold mechano-receptors (LTMs). Last, we found that the central and peripheral projections of mechanoreceptive DRG neurons were compromised in c-Maf deletion mice. Together, our results indicate that c-Maf is required for the proper development of MafA (+)/Ret (+)/GFR alpha 2 (+) LTMs in the DRG, their afferent projections in the dorsal horn and Pacinian corpuscles, as well as neurons in laminae III/IV of the spinal cord.