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Sprouty2 down-regulation promotes axon growth by adult sensory neurons

Barbara Hausott1, Natalie Vallant, Maria Auer

  • 1Division of Neuroanatomy, Innsbruck Medical University, Muellerstrasse 59, A-6020 Innsbruck, Austria.

Molecular and Cellular Neurosciences
|August 18, 2009
PubMed

Insights

Down-regulating Sprouty2 in adult sensory neurons promotes axon growth by activating the Ras/Raf/ERK pathway. This finding offers potential therapeutic targets for nerve repair and regeneration.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Fibroblast growth factors (FGFs) are crucial for axonal growth and repair.
  • The Ras/Raf/ERK pathway, activated by FGFs, promotes peripheral axon regeneration.
  • Sprouty proteins act as negative feedback inhibitors of this pathway.

Purpose of the Study:

  • To investigate Sprouty isoform expression in adult dorsal root ganglia (DRG) sensory neurons.
  • To determine the effect of Sprouty inhibition on axon growth in these neurons.

Main Methods:

  • Quantified Sprouty isoform expression in adult DRG neurons.
  • Utilized small interfering RNAs (siRNAs) to down-regulate Sprouty2.
  • Assessed axon growth and ERK/Ras pathway activation.

Main Results:

  • Sprouty2 showed the highest expression in DRG neurons.
  • Down-regulation of Sprouty2 significantly promoted axon elongation.
  • Sprouty2 overexpression inhibited axon growth.
  • Sprouty2 levels were unchanged in vivo after sciatic nerve injury.

Conclusions:

  • Sprouty2 is highly expressed in adult peripheral sensory neurons.
  • Inhibiting Sprouty2 enhances FGF-2-induced Ras/Raf/ERK pathway activation and promotes axon growth.
  • Sprouty2 down-regulation is a promising strategy for enhancing peripheral nerve regeneration.

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