List of cDNAs used for in situ hybridization.

Unlike immature neurons and the ones from the peripheral nervous system (PNS), mature neurons from the central nervous system (CNS) cannot regenerate after injury. In the past 15 years, tremendous progress has been made to identify molecules and pathways necessary for neuroprotection and/or axon regeneration after CNS injury. In most regenerative models, phosphorylated ribosomal protein S6 (p-RPS6) is up-regulated in neurons, which is often associated with an activation of the mTOR (mammalian target of rapamycin) pathway. However, the exact contribution of posttranslational modifications of this ribosomal protein in CNS regeneration remains elusive. In this study, we demonstrate that RPS6 phosphorylation is essential for PNS and CNS regeneration in mice. We show that this phosphorylation is induced during the preconditioning effect in dorsal root ganglion (DRG) neurons and that it is controlled by the p90S6 kinase RSK2. Our results reveal that RSK2 controls the preconditioning effect and that the RSK2-RPS6 axis is key for this process, as well as for PNS regeneration. Finally, we demonstrate that RSK2 promotes CNS regeneration in the dorsal column, spinal cord synaptic plasticity, and target innervation leading to functional recovery. Our data establish the critical role of RPS6 phosphorylation controlled by RSK2 in CNS regeneration and give new insights into the mechanisms related to axon growth and circuit formation after traumatic lesion.与未成熟神经元以及外周神经系统（peripheral nervous system, PNS）的神经元不同，中枢神经系统（central nervous system, CNS）的成熟神经元在损伤后无法实现再生。近十五年来，学界在鉴定中枢神经系统损伤后介导神经保护和/或轴突再生的分子与通路方面取得了显著进展。在多数再生模型中，磷酸化核糖体蛋白S6（phosphorylated ribosomal protein S6, p-RPS6）在神经元内表达上调，这一现象通常与雷帕霉素靶蛋白（mammalian target of rapamycin, mTOR）通路的激活密切相关。然而，该核糖体蛋白的翻译后修饰在中枢神经系统再生中的确切贡献仍未明晰。本研究证实，在小鼠体内，RPS6磷酸化对于外周神经系统与中枢神经系统的再生均不可或缺。研究发现，该磷酸化过程在背根神经节（dorsal root ganglion, DRG）神经元的预适应效应期间被诱导，并由p90S6激酶RSK2调控。研究结果表明，RSK2介导了预适应效应，且RSK2-RPS6信号轴不仅是该过程的关键调控通路，同时也是外周神经系统再生的关键调控通路。最后，本研究证实RSK2可促进脊髓背柱的中枢神经系统再生、脊髓突触可塑性以及靶组织神经支配，最终推动功能恢复。本研究数据明确了RSK2调控的RPS6磷酸化在中枢神经系统再生中的关键作用，并为创伤性损伤后轴突生长与神经环路形成的相关机制提供了全新的研究视角。