c-Maf–/–中RA機(jī)械感覺(jué)神經(jīng)元向中樞脊髓背角III/IV層神經(jīng)元的投射異常,。
4月18號(hào)，《神經(jīng)科學(xué)雜志》(The Journal of Neuroscience) 發(fā)表了中科院上海生科院神經(jīng)所神經(jīng)發(fā)育及其調(diào)控機(jī)理研究組的論文《c-Maf is required for the development of dorsal horn laminae III/IV neurons and mechanoreceptive DRG axon projections》,。該項(xiàng)工作是由博士研究生胡佳和黃天文等在程樂(lè)平研究員的指導(dǎo)下共同完成的,。同期的The Journal of Neuroscience發(fā)表了題為“c-Maf 幫助決定RA傳入纖維命運(yùn)”（c-Maf Helps Specify RA Afferent Fate）的評(píng)論，對(duì)該項(xiàng)工作進(jìn)行了介紹,。
正常的軀體感覺(jué)依賴于外周背根神經(jīng)節(jié)（DRG）及其投射區(qū)–脊髓背角神經(jīng)元間建立精確的連接,。機(jī)械刺激（包括物體質(zhì)地、形狀,、振動(dòng)及壓力等信息）被外周感覺(jué)小體中的DRG機(jī)械感覺(jué)神經(jīng)元接收,，并向中樞投射至脊髓背角的III/IV層及腦形成觸壓覺(jué)。目前已知一些分子在脊髓背角神經(jīng)元,、感知痛覺(jué)及本體感覺(jué)的DRG神經(jīng)元的發(fā)育中發(fā)揮重要作用,。然而，關(guān)于參與形成觸壓覺(jué)的脊髓背角III/IV層神經(jīng)元及DRG中低閾值的機(jī)械感覺(jué)神經(jīng)元（low-threshold mechanoreceptor, LTM）的發(fā)育,，目前的報(bào)道還很少,。利用原位雜交及免疫組化染色等技術(shù)，作者發(fā)現(xiàn)轉(zhuǎn)錄因子c-Maf特異表達(dá)在脊髓背角的III/IV層神經(jīng)元及背根神經(jīng)節(jié)有髓鞘的中大直徑神經(jīng)元中,。通過(guò)分析敲除小鼠的表型,，發(fā)現(xiàn)c-Maf 調(diào)控脊髓背角III/IV層神經(jīng)元的發(fā)育,。進(jìn)一步實(shí)驗(yàn)表明，c-Maf 基因敲除特異影響表達(dá)MafA,、Ret及GFRα2的快適應(yīng)性（rapidly adapting, RA）LTM的發(fā)育及其向中樞脊髓背角III/IV層神經(jīng)元與外周帕西尼氏小體（Pacinian corpuscles）的投射,。該研究結(jié)果揭示了轉(zhuǎn)錄因子c-Maf在脊髓背角III/IV層神經(jīng)元發(fā)育、背根神經(jīng)節(jié)RA LTM的發(fā)育及其投射建立中的重要作用,。
該工作得到了科技部及中科院項(xiàng)目的資助,。(生物谷：Bioon.com)
doi:10.1523/JNEUROSCI.6239-11.2012
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c-Maf Is Required for the Development of Dorsal Horn Laminae III/IV Neurons and Mechanoreceptive DRG Axon Projections
Jia Hu, Tianwen Huang, Tingting Li, Zhen Guo, and Leping Cheng
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, GABAA receptor subunit α5, and neuropeptide cholecystokinin. In addition, among the four major subpopulations of DRG neurons marked by expression of TrkA, TrkB, TrkC, and MafA/GFRα2/Ret, c-Maf was required selectively for the proper differentiation of MafA+/Ret+/GFRα2+ low-threshold mechanoreceptors (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+/GFRα2+ 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.
