Transcriptional and post-transcriptional regulation of a brain growth protein: Regional differentiation and regeneration induction of GAP-43

Uk Namgung, Aryeh Routtenberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

During axonal regeneration synthesis of different growth-associated proteins is increased. As yet there is no clear picture of the specific contribution made by the transcriptional and post-transcriptional machinery that provides the gene products necessary for process outgrowth. Here we focus our study on the transcriptional processes in neurons by using intron-directed in situ hybridization to the primary transcript of a brain growth protein GAP-43. In most brain regions, levels of primary transcript expression of GAP-43 were highly correlated with levels of its mRNA. However, there were notable dissociations: in hippocampal granule cells, high levels of primary transcript were evident yet no GAP-43 mRNA was detected. In locus coeruleus the reverse was true; there were high levels of GAP-43 mRNA but no detectable primary transcript. A primary transcript antitermination mechanism is proposed to explain the first dissociation, and a post-transcriptional mRNA stabilization mechanism to explain the second. Transcriptional activation during nerve regeneration was monitored by assessing primary transcript induction of GAP-43 in mouse facial motor neurons. This induction, as well as its mRNA, was restricted to the side of the facial nerve crush. Increases were first observed at 24 h with a rapid increase in both measures up to 3 days. To our knowledge, this is the first in vivo evidence demonstrating transcriptional activation of a brain growth protein in regenerating neurons. The present study points to the GAP-43 transcriptional mechanism as a key determinant of GAP-43 synthesis. Along with the recruitment of post-transcriptional mechanisms, such synthesis occurs in response to both intrinsic developmental programs and extrinsic environmental signals.

Original languageEnglish (US)
Pages (from-to)3124-3136
Number of pages13
JournalEuropean Journal of Neuroscience
Volume12
Issue number9
DOIs
StatePublished - Oct 17 2000

Keywords

  • Facial neuron
  • In situ hybridization
  • Intronic sequences
  • Nerve crush
  • Primary transcript
  • Transcription

ASJC Scopus subject areas

  • Neuroscience(all)

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