Chandran Vijayendran, Coppola Giovanni, Nawabi Homaira, Omura Takao, Versano Revital, Huebner Eric A, Zhang Alice, Costigan Michael, Yekkirala Ajay, Barrett Lee, Blesch Armin, Michaelevski Izhak, Davis-Turak Jeremy, Gao Fuying, Langfelder Peter, Horvath Steve, He Zhigang, Benowitz Larry, Fainzilber Mike, Tuszynski Mark, Woolf Clifford J, Geschwind Daniel H
Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Neuron. 2016 Mar 2;89(5):956-70. doi: 10.1016/j.neuron.2016.01.034. Epub 2016 Feb 18.
The regenerative capacity of the injured CNS in adult mammals is severely limited, yet axons in the peripheral nervous system (PNS) regrow, albeit to a limited extent, after injury. We reasoned that coordinate regulation of gene expression in injured neurons involving multiple pathways was central to PNS regenerative capacity. To provide a framework for revealing pathways involved in PNS axon regrowth after injury, we applied a comprehensive systems biology approach, starting with gene expression profiling of dorsal root ganglia (DRGs) combined with multi-level bioinformatic analyses and experimental validation of network predictions. We used this rubric to identify a drug that accelerates DRG neurite outgrowth in vitro and optic nerve outgrowth in vivo by inducing elements of the identified network. The work provides a functional genomics foundation for understanding neural repair and proof of the power of such approaches in tackling complex problems in nervous system biology.
成年哺乳动物中受损的中枢神经系统（CNS）的再生能力受到严重限制，然而，外周神经系统（PNS）中的轴突在损伤后虽再生程度有限，但仍会生长。我们推断，涉及多条途径的受损神经元中基因表达的协调调控是PNS再生能力的核心。为了提供一个揭示损伤后PNS轴突再生所涉及途径的框架，我们应用了一种全面的系统生物学方法，首先对背根神经节（DRG）进行基因表达谱分析，并结合多层次生物信息学分析以及对网络预测的实验验证。我们使用这个准则来鉴定一种药物，该药物通过诱导所鉴定网络的元件来加速体外DRG神经突生长和体内视神经生长。这项工作为理解神经修复提供了功能基因组学基础，并证明了此类方法在解决神经系统生物学复杂问题方面的强大力量。
