Peripheral NT3 signaling is required for ETS protein expression and central patterning of proprioceptive sensory afferents
Peripheral NT3 signaling is required for ETS protein expression and central patterning of proprioceptive sensory afferents
复制标题
DOI：
10.1016/s0896-6273(03)00261-7
复制
发表时间：
2003-05-08
期刊：
影响因子：
16.2
通讯作者：
Snider, WD
中科院分区：
文献类型：
--
作者：
Patel, TD;Kramer, I;Snider, WD
为了研究NT 3在引导本体感受背根神经节（DRG）神经元的轴突投射中的作用，将NT 3（-/-）小鼠与携带促凋亡基因Bax的靶向缺失的小鼠杂交。在Bax（-/-）/NT 3（-/-）小鼠中，NT 3依赖性神经元存活并表达本体感受神经元标记物小清蛋白。本体感受轴突进入脊髓的初始延伸和侧支化正常发生，但本体感受轴突仅延伸至中间脊髓。这种投射缺陷类似于缺乏ETS转录因子ER 81的小鼠中的缺陷（Arber等人，2000）。来自Sax（-/-）/NT 3-/小鼠的DRG神经元很少表达ER 81蛋白。肌肉中NT 3转基因的表达恢复了NTZ 3（-/-）小鼠中DRG ER 81的表达。最后，将NT 3添加到DRG外植体培养物中导致ER 81蛋白的诱导。我们的数据表明，NT 3介导的本体感觉传入运动神经元连接的形成，通过调节ER 81。
To study the role of NT3 in directing axonal projections of proprioceptive dorsal root ganglion (DRG) neurons, NT3(-/-) mice were crossed with mice carrying a targeted deletion of the proapoptotic gene Bax. In Bax(-/-)/NT3(-/-) mice, NT3-dependent neurons survived and expressed the proprioceptive neuronal marker parvalbumin. Initial extension and collateralization of proprioceptive axons into the spinal cord occurred normally, but proprioceptive axons extended only as far as the intermediate spinal cord. This projection defect is similar to the defect in mice lacking the ETS transcription factor ER81 (Arber et al., 2000). Few if any DRG neurons from Sax(-/-)/NT3-/mice expressed ER81 protein. Expression of a NT3 transgene in muscle restored DRG ER81 expression in NTZ3(-/-) mice. Finally, addition of NT3 to DRG explant cultures resulted in induction of ER81 protein. Our data indicate that NT3 mediates the formation of proprioceptive afferent-motor neuron connections via regulation of ER81.