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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism
  • Axons / physiology*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • Disease Models, Animal
  • Ganglia, Spinal / cytology*
  • 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
  • Nerve Regeneration / physiology*
  • Neurons / cytology*
  • Nitrogenous Group Transferases / genetics
  • Nitrogenous Group Transferases / metabolism
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Peripheral Nervous System Diseases / physiopathology*
  • cdc42 GTP-Binding Protein / genetics
  • cdc42 GTP-Binding Protein / metabolism


  • Antigens, Neoplasm
  • Cell Adhesion Molecules
  • FXYD5 protein, mouse
  • Ion Channels
  • Membrane Glycoproteins
  • Membrane Proteins
  • Microfilament Proteins
  • TROP2 protein, mouse
  • Nitrogenous Group Transferases
  • Gfpt1 protein, mouse
  • Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
  • PTEN Phosphohydrolase
  • cdc42 GTP-Binding Protein