(The Rockefeller University Press, 2014) O’Donovan, Kevin J.; Ma, Kaijie; Guo, Hengchang; Wang, Chen; Sun, Fang; Han, Seung Baek; Kim, Hyukmin; Wong, Jamie K.; Charron, Jean; Zou, Hongyan; Son, Young-Jin; He, Zhigang; Zhong, Jian
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.
