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Carmel JB, Young W, Hart RP. Flipping the transcriptional switch from myelin inhibition to axon growth in the CNS. Front Mol Neurosci. 2015;8:34doi: 10.3389/fnmol.2015.00034.
Carmel, J. B., Young, W., & Hart, R. P. (2015). Flipping the transcriptional switch from myelin inhibition to axon growth in the CNS. Frontiers in molecular neuroscience, 834. https://doi.org/10.3389/fnmol.2015.00034
Carmel, Jason B, et al. "Flipping the transcriptional switch from myelin inhibition to axon growth in the CNS." Frontiers in molecular neuroscience vol. 8 (2015): 34. doi: https://doi.org/10.3389/fnmol.2015.00034
Carmel JB, Young W, Hart RP. Flipping the transcriptional switch from myelin inhibition to axon growth in the CNS. Front Mol Neurosci. 2015 Jul 17;8:34. doi: 10.3389/fnmol.2015.00034. eCollection 2015. PMID: 26236189; PMCID: PMC4505142.
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Front Mol Neurosci. 2015 Jul 17;8:34. doi: 10.3389/fnmol.2015.00034. eCollection 2015.

Flipping the transcriptional switch from myelin inhibition to axon growth in the CNS.

Frontiers in molecular neuroscience

Jason B Carmel, Wise Young, Ronald P Hart

Affiliations

  1. Brain Mind Research Institute and Departments of Pediatrics and Neurology, Weill Cornell Medical College New York, NY, USA ; Burke-Cornell Medical Research Institute White Plains, NY, USA.
  2. W.M. Keck Center for Collaborative Neuroscience and the Department of Cell Biology and Neuroscience, Rutgers University Piscataway, NJ, USA.

PMID: 26236189 PMCID: PMC4505142 DOI: 10.3389/fnmol.2015.00034

Abstract

Poor regeneration of severed axons in the central nervous system (CNS) limits functional recovery. Regeneration failure involves interplay of inhibitory environmental elements and the growth state of the neuron. To find internal changes in gene expression that might overcome inhibitory environmental cues, we compared several paradigms that allow growth in the inhibitory environment. Conditions that allow axon growth by axotomized and cultured dorsal root ganglion (DRG) neurons on CNS myelin include immaturity (the first few postnatal days), high levels of cyclic adenosine mono phosphate (cAMP), and conditioning with a peripheral nerve lesion before explant. This shift from inhibition to growth depends on transcription. Seeking to understand the transcriptome changes that allow axon growth in the CNS, we collaborated with the Marie Filbin laboratory to identify several mRNAs that are functionally relevant, as determined by gain- and loss-of-function studies. In this Perspective, we review evidence from these experiments and discuss the merits of comparing multiple regenerative paradigms to identify a core transcriptional program for CNS axon regeneration.

Keywords: DRG; IL-6; SLPI; axon growth; mRNA expression; metallothionein

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