1. A Systems-Level Analysis of the Peripheral Nerve Intrinsic Axonal Growth Program.
- Author
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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, and Geschwind DH
- Subjects
- Animals, Animals, Newborn, Antigens, Neoplasm genetics, Antigens, Neoplasm metabolism, Cell Adhesion Molecules genetics, Cell Adhesion Molecules metabolism, Cells, Cultured, Chromatin Immunoprecipitation, Disease Models, Animal, Gene Expression Regulation genetics, Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing), Ion Channels, Membrane Glycoproteins genetics, Membrane Glycoproteins metabolism, Membrane Proteins genetics, Membrane Proteins metabolism, Mice, Mice, Inbred C57BL, Microfilament Proteins, Nerve Regeneration genetics, Nitrogenous Group Transferases genetics, Nitrogenous Group Transferases metabolism, PTEN Phosphohydrolase genetics, PTEN Phosphohydrolase metabolism, cdc42 GTP-Binding Protein genetics, cdc42 GTP-Binding Protein metabolism, Axons physiology, Ganglia, Spinal cytology, Nerve Regeneration physiology, Neurons cytology, Peripheral Nervous System Diseases physiopathology
- 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., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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