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. 2012 Jan 12;4:60.
doi: 10.3389/fnmol.2011.00060. eCollection 2011.

Tuning the Orchestra: Transcriptional Pathways Controlling Axon Regeneration

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Free PMC article

Tuning the Orchestra: Transcriptional Pathways Controlling Axon Regeneration

Andrea Tedeschi. Front Mol Neurosci. .
Free PMC article

Abstract

Trauma in the adult mammalian central nervous system leads to irreversible structural and functional impairment due to failed regeneration attempts. In contrast, neurons in the peripheral nervous system exhibit a greater regenerative ability. It has been proposed that an orchestrated sequence of transcriptional events controlling the expression of specific sets of genes may be the underlying basis of an early cell-autonomous regenerative response. Understanding whether transcriptional fine tuning, in parallel with strategies aimed at counteracting extrinsic impediments promotes axon re-growth following central nervous system injuries represents an exciting challenge for future studies. Transcriptional pathways controlling axon regeneration are presented and discussed in this review.

Keywords: axonal regeneration; epigenetic changes; network; transcription factors and co-activators; transcriptional pathways.

Figures

Figure 1
Figure 1
Gene transcription is a highly regulated process. DNA is wrapped around histones in chromatin (upper box). Several modifying complexes remodel chromatin and modify histones. Both DNA and histone tails undergo post translational modifications (Ac, acetylation; Me, methylation; P, phosphorylation) that ultimately shape chromatin architecture in a more or less favorable environment promoting or inhibiting transcription respectively. Transcription starts when TFs and co-activators bind to specific DNA regulatory elements upstream to the transcriptional start site (TSS) and recruit RNA polymerase II.
Figure 2
Figure 2
Schematic diagram summarizing transcriptional pathways involved in peripheral nerve regeneration. After peripheral nerve injury, activation of early clusters of TFs occurs through coordinated sequences of intracellular cascades. Upon activation, TFs and co-activators translocate to the nucleus where they bind to regulatory regions of regenerative-associated genes to drive their expression as part of an early pro-regenerative program (P, phosphorylation; Ac, acetylation; ERK, extracellular-signal-regulated kinase; p38, p38-mitogen-activated protein kinase).
Figure 3
Figure 3
Transcriptional network. (A) List of various transcription regulators, chromatin remodelers, acetyltransferases, kinases, and growth factors implicated in an early regenerative response after nerve injury. (B) Ingenuity generated screenshot of a regenerative-associated transcriptional network. Connecting arrows and lines represent interactions between nodes.

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