Peripheral nervous system genes expressed in central neurons induce growth on inhibitory substrates

PLoS One. 2012;7(6):e38101. doi: 10.1371/journal.pone.0038101. Epub 2012 Jun 6.

Abstract

Trauma to the spinal cord and brain can result in irreparable loss of function. This failure of recovery is in part due to inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans (CSPGs). Peripheral nervous system (PNS) neurons exhibit increased regenerative ability compared to central nervous system neurons, even in the presence of inhibitory environments. Previously, we identified over a thousand genes differentially expressed in PNS neurons relative to CNS neurons. These genes represent intrinsic differences that may account for the PNS's enhanced regenerative ability. Cerebellar neurons were transfected with cDNAs for each of these PNS genes to assess their ability to enhance neurite growth on inhibitory (CSPG) or permissive (laminin) substrates. Using high content analysis, we evaluated the phenotypic profile of each neuron to extract meaningful data for over 1100 genes. Several known growth associated proteins potentiated neurite growth on laminin. Most interestingly, novel genes were identified that promoted neurite growth on CSPGs (GPX3, EIF2B5, RBMX). Bioinformatic approaches also uncovered a number of novel gene families that altered neurite growth of CNS neurons.

Publication types

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

MeSH terms

  • Cerebellum / cytology
  • Chondroitin Sulfate Proteoglycans
  • Computational Biology
  • DNA, Complementary / genetics
  • Gene Expression Regulation / genetics*
  • Humans
  • Laminin
  • Microarray Analysis
  • Nerve Regeneration / genetics*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurites / physiology
  • Neurons / metabolism
  • Peripheral Nervous System / cytology
  • Peripheral Nervous System / metabolism*
  • Phenotype
  • Signal Transduction / genetics

Substances

  • Chondroitin Sulfate Proteoglycans
  • DNA, Complementary
  • Laminin
  • Nerve Tissue Proteins