CNS repair and axon regeneration: Using genetic variation to determine mechanisms

Exp Neurol. 2017 Jan;287(Pt 3):409-422. doi: 10.1016/j.expneurol.2016.05.004. Epub 2016 May 6.


The importance of genetic diversity in biological investigation has been recognized since the pioneering studies of Gregor Johann Mendel and Charles Darwin. Research in this area has been greatly informed recently by the publication of genomes from multiple species. Genes regulate and create every part and process in a living organism, react with the environment to create each living form and morph and mutate to determine the history and future of each species. The regenerative capacity of neurons differs profoundly between animal lineages and within the mammalian central and peripheral nervous systems. Here, we discuss research that suggests that genetic background contributes to the ability of injured axons to regenerate in the mammalian central nervous system (CNS), by controlling the regulation of specific signaling cascades. We detail the methods used to identify these pathways, which include among others Activin signaling and other TGF-β superfamily members. We discuss the potential of altering these pathways in patients with CNS damage and outline strategies to promote regeneration and repair by combinatorial manipulation of neuron-intrinsic and extrinsic determinants.

Keywords: Activin/TGF-β signaling; CAST/Ei; CNS regeneration; Collaborative cross; Congenics; Genetic background; Neuron-intrinsic and extrinsic factors.

Publication types

  • Review

MeSH terms

  • Animals
  • Axons / pathology
  • Axons / physiology*
  • Central Nervous System Diseases* / genetics
  • Central Nervous System Diseases* / pathology
  • Central Nervous System Diseases* / physiopathology
  • Genetic Variation / genetics*
  • Humans
  • Nerve Regeneration / physiology*
  • Signal Transduction / physiology