Deletion of Nf1 in neurons induces increased axon collateral branching after dorsal root injury

Mario I. Romero, Lu Lin, Mark E. Lush, Lei Lei, Luis F. Parada, Yuan Zhu

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Ras-mediated signaling pathways participate in multiple aspects of neural development and function. For example, Ras signaling lies downstream of neurotrophic factors and Trk family receptor tyrosine kinases to regulate neuronal survival and morphological differentiation, including axon extension and target innervation. Neurofibromin, the protein encoded by the tumor suppressor gene Nf1, is a negative regulator of Ras [Ras-GAP (GTPase-activating protein)], and we previously demonstrated that Nf1 null embryonic sensory and sympathetic neurons can survive and differentiate independent of neurotrophin support. In this report, we demonstrate that Nf1 loss in adult sensory neurons enhances their intrinsic capacity for neurite outgrowth and collateral branching in vitro and in vivo after dorsal root injury. In contrast to the permanent sensory deficits observed in control mice after dorsal rhizotomy, neuron-specific Nf1 mutant mice spontaneously recover proprioceptive function. This phenomenon appears to be mediated both by a cell-autonomous capacity of spared Nf1-/- DRG neurons for increased axonal sprouting, and by non-cell-autonomous contribution from Nf1-/- neurons in the denervated spinal cord.

Original languageEnglish (US)
Pages (from-to)2124-2134
Number of pages11
JournalJournal of Neuroscience
Volume27
Issue number8
DOIs
StatePublished - Feb 21 2007

Fingerprint

Spinal Nerve Roots
ras GTPase-Activating Proteins
Axons
Nerve Growth Factors
Sensory Receptor Cells
Neurons
Wounds and Injuries
Neurofibromin 1
Rhizotomy
Diagnosis-Related Groups
Receptor Protein-Tyrosine Kinases
Tumor Suppressor Genes
Spinal Cord
Proteins

Keywords

  • Collateral branching
  • Dorsal rhizotomy
  • Functional recovery
  • Neurofibromin
  • NT-3
  • Regeneration

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Deletion of Nf1 in neurons induces increased axon collateral branching after dorsal root injury. / Romero, Mario I.; Lin, Lu; Lush, Mark E.; Lei, Lei; Parada, Luis F.; Zhu, Yuan.

In: Journal of Neuroscience, Vol. 27, No. 8, 21.02.2007, p. 2124-2134.

Research output: Contribution to journalArticle

Romero, Mario I. ; Lin, Lu ; Lush, Mark E. ; Lei, Lei ; Parada, Luis F. ; Zhu, Yuan. / Deletion of Nf1 in neurons induces increased axon collateral branching after dorsal root injury. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 8. pp. 2124-2134.
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