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 Tuszynski

Clifford J. Woolf, Daniel H. Geschwind

Research output: Contribution to journal › Article › peer-review

290 Scopus citations

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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title = "A Systems-Level Analysis of the Peripheral Nerve Intrinsic Axonal Growth Program",

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.",

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

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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 - Huebner, Eric A.

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AU - Langfelder, Peter

AU - Horvath, Steve

AU - He, Zhigang

AU - Benowitz, Larry

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AU - Geschwind, Daniel H.

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

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