The transcription factor ATF-3 promotes neurite outgrowth

Mol Cell Neurosci. May-Jun 2006;32(1-2):143-54. doi: 10.1016/j.mcn.2006.03.005. Epub 2006 May 19.

Abstract

Dorsal root ganglion (DRG) neurons regenerate after a peripheral nerve injury but not after injury to their axons in the spinal cord. A key question is which transcription factors drive the changes in gene expression that increase the intrinsic growth state of peripherally injured sensory neurons? A prime candidate is activating transcription factor-3 (ATF-3), a transcription factor that we find is induced in all DRG neurons after peripheral, but not central axonal injury. Moreover, we show in adult DRG neurons that a preconditioning peripheral, but not central axonal injury, increases their growth, correlating closely with the pattern of ATF-3 induction. Using viral vectors, we delivered ATF-3 to cultured adult DRG neurons and find that ATF-3 enhances neurite outgrowth. Furthermore, ATF-3 promotes long sparsely branched neurites. ATF-3 overexpression did not increase c-Jun expression. ATF-3 may contribute, therefore, to neurite outgrowth by orchestrating the gene expression responses in injured neurons.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Activating Transcription Factor 3 / genetics
  • Activating Transcription Factor 3 / metabolism*
  • Animals
  • Cells, Cultured
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / injuries
  • Ganglia, Spinal / metabolism*
  • Gene Expression Regulation / physiology
  • Genetic Vectors / physiology
  • Growth Cones / metabolism
  • Growth Cones / ultrastructure
  • Nerve Regeneration / genetics*
  • Neurites / metabolism*
  • Neurites / ultrastructure
  • Neurons, Afferent / cytology
  • Neurons, Afferent / metabolism*
  • Peripheral Nerve Injuries
  • Peripheral Nerves / cytology
  • Peripheral Nerves / metabolism*
  • Proto-Oncogene Proteins c-jun / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Rhizotomy / adverse effects
  • Spinal Nerve Roots / cytology
  • Spinal Nerve Roots / injuries
  • Spinal Nerve Roots / metabolism
  • Up-Regulation / physiology

Substances

  • Activating Transcription Factor 3
  • Atf3 protein, rat
  • Proto-Oncogene Proteins c-jun