B-RAF kinase drives developmental axon growth and promotes axon regeneration in the injured mature CNS

Kevin J. O'Donovan, Kaijie Ma, Hengchang Guo, Chen Wang, Fang Sun, Seung Baek Han, Hyukmin Kim, Jamie K. Wong, Jean Charron, Hongyan Zou, Young Jin Son, Zhigang He, Jian Zhong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Activation of intrinsic growth programs that promote developmental axon growth may also facilitate axon regeneration in injured adult neurons. Here, we demonstrate that conditional activation of B-RAF kinase alone in mouse embryonic neurons is sufficient to drive the growth of long-range peripheral sensory axon projections in vivo in the absence of upstream neurotrophin signaling. We further show that activated B-RAF signaling enables robust regenerative growth of sensory axons into the spinal cord after a dorsal root crush as well as substantial axon regrowth in the crush-lesioned optic nerve. Finally, the combination of B-RAF gain-of-function and PTEN loss-of-function promotes optic nerve axon extension beyond what would be predicted for a simple additive effect. We conclude that cell-intrinsic RAF signaling is a crucial pathway promoting developmental and regenerative axon growth in the peripheral and central nervous systems.

Original languageEnglish (US)
Pages (from-to)801-814
Number of pages14
JournalJournal of Experimental Medicine
Volume211
Issue number5
DOIs
StatePublished - May 2014
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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