A Systems-Level Analysis of the Peripheral Nerve Intrinsic Axonal Growth Program

Vijayendran Chandran; Giovanni Coppola; Homaira Nawabi; Takao Omura; Revital Versano; Eric A. Huebner; Alice Zhang; Michael Costigan; Ajay Yekkirala; Lee Barrett; Armin Blesch; Izhak Michaelevski; Jeremy Davis-Turak; Fuying Gao; Peter Langfelder; Steve Horvath; Zhigang He; Larry Benowitz; Mike Fainzilber; Mark Tuszynski; Clifford J. Woolf; Daniel H. Geschwind

doi:10.1016/j.neuron.2016.01.034

A Systems-Level Analysis of the Peripheral Nerve Intrinsic Axonal Growth Program

Vijayendran Chandran, Giovanni Coppola, Homaira Nawabi, Takao Omura, Revital Versano, Eric A. Huebner, Alice Zhang, Michael Costigan, Ajay Yekkirala, Lee Barrett, Armin Blesch, Izhak Michaelevski, Jeremy Davis-Turak, Fuying Gao, Peter Langfelder, Steve Horvath, Zhigang He, Larry Benowitz, Mike Fainzilber, Mark TuszynskiClifford J. Woolf, Daniel H. Geschwind

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Abstract

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.

Original language	English
Pages (from-to)	956-970
Number of pages	15
Journal	Neuron
Volume	89
Issue number	5
DOIs	https://doi.org/10.1016/j.neuron.2016.01.034
State	Published - 2 Mar 2016
Externally published	Yes

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Chandran, V., Coppola, G., Nawabi, H., Omura, T., Versano, R., Huebner, E. A., Zhang, A., Costigan, M., Yekkirala, A., Barrett, L., Blesch, A., Michaelevski, I., Davis-Turak, J., Gao, F., Langfelder, P., Horvath, S., He, Z., Benowitz, L., Fainzilber, M., ... Geschwind, D. H. (2016). A Systems-Level Analysis of the Peripheral Nerve Intrinsic Axonal Growth Program. Neuron, 89(5), 956-970. https://doi.org/10.1016/j.neuron.2016.01.034

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abstract = "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.",

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Chandran, V, Coppola, G, Nawabi, H, Omura, T, Versano, R, Huebner, EA, Zhang, A, Costigan, M, Yekkirala, A, Barrett, L, Blesch, A, Michaelevski, I, Davis-Turak, J, Gao, F, Langfelder, P, Horvath, S, He, Z, Benowitz, L, Fainzilber, M, Tuszynski, M, Woolf, CJ & Geschwind, DH 2016, 'A Systems-Level Analysis of the Peripheral Nerve Intrinsic Axonal Growth Program', Neuron, vol. 89, no. 5, pp. 956-970. https://doi.org/10.1016/j.neuron.2016.01.034

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AU - Gao, Fuying

AU - Langfelder, Peter

AU - Horvath, Steve

AU - He, Zhigang

AU - Benowitz, Larry

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AU - Woolf, Clifford J.

AU - Geschwind, Daniel H.

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A Systems-Level Analysis of the Peripheral Nerve Intrinsic Axonal Growth Program

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