Role of motoneuron-derived neurotrophin 3 in survival and axonal projection of sensory neurons during neural circuit formation
Role of motoneuron-derived neurotrophin 3 in survival and axonal projection of sensory neurons during neural circuit formation
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DOI：
10.1242/dev.069997
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发表时间：
2012-03-15
期刊：
影响因子：
4.6
通讯作者：
Takebayashi, Hirohide
中科院分区：
文献类型：
--
作者：
Usui, Noriyoshi;Watanabe, Keisuke;Takebayashi, Hirohide
感觉神经元具有中枢和外周分支，在发育过程中与运动神经元形成独特的脊髓神经回路。感觉轴突的外周分支与从中枢神经系统（CNS）向外周肌肉延伸的运动轴突相束，而本体感觉神经元的中心分支直接支配运动神经元。尽管解剖学上有很好的记录，但神经回路形成过程中感觉-运动相互作用的分子机制尚未完全了解。为了研究运动神经元在感觉神经元发育中的作用，我们分析了Olig2敲除（KO）小鼠胚胎背根神经节（DRG）中缺乏运动神经元的感觉神经元表型。我们发现，在胚胎日(E) 10.5时，Olig2 KO胚胎DRG中凋亡细胞数量增加。此外，在E10.5时外周分支和E15.5时中央分支的感觉神经元轴突均出现异常。为了了解调节感觉神经元发育的运动神经元衍生因子，我们重点研究了神经营养因子3 (Ntf3; NT-3)，因为Ntf3及其受体（Trk）分别在运动神经元和感觉神经元中强烈表达。利用Ntf3条件敲除（Ntf3 conditional knockout, cKO）胚胎分析运动神经元来源的Ntf3的意义，我们观察到支配运动神经元的中央分支凋亡增加和异常投射，表型与Olig2 KO胚胎明显相似。综上所述，我们表明运动神经元是Ntf3的功能来源，运动神经元衍生的Ntf3是感觉神经元存活和轴突投射必不可少的靶前神经营养因子。
Sensory neurons possess the central and peripheral branches and they form unique spinal neural circuits with motoneurons during development. Peripheral branches of sensory axons fasciculate with the motor axons that extend toward the peripheral muscles from the central nervous system (CNS), whereas the central branches of proprioceptive sensory neurons directly innervate motoneurons. Although anatomically well documented, the molecular mechanism underlying sensory-motor interaction during neural circuit formation is not fully understood. To investigate the role of motoneuron on sensory neuron development, we analyzed sensory neuron phenotypes in the dorsal root ganglia (DRG) of Olig2 knockout (KO) mouse embryos, which lack motoneurons. We found an increased number of apoptotic cells in the DRG of Olig2 KO embryos at embryonic day (E) 10.5. Furthermore, abnormal axonal projections of sensory neurons were observed in both the peripheral branches at E10.5 and central branches at E15.5. To understand the motoneuron-derived factor that regulates sensory neuron development, we focused on neurotrophin 3 (Ntf3; NT-3), because Ntf3 and its receptors (Trk) are strongly expressed in motoneurons and sensory neurons, respectively. The significance of motoneuron-derived Ntf3 was analyzed using Ntf3 conditional knockout (cKO) embryos, in which we observed increased apoptosis and abnormal projection of the central branch innervating motoneuron, the phenotypes being apparently comparable with that of Olig2 KO embryos. Taken together, we show that the motoneuron is a functional source of Ntf3 and motoneuron-derived Ntf3 is an essential pre-target neurotrophin for survival and axonal projection of sensory neurons.