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Extracellular signal‐regulated kinases 1/2 are required for adult retinal ganglion cell axon regeneration induced by fibroblast growth factor‐2
Author(s) -
Sapieha Przemyslaw S.,
Hauswirth William W.,
Di Polo Adriana
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20803
Subject(s) - axon , fibroblast growth factor , microbiology and biotechnology , neurotrophic factors , biology , retinal ganglion cell , neuroscience , signal transduction , neurotrophin , fibroblast growth factor receptor , regeneration (biology) , retina , receptor , biochemistry
The intracellular signaling mechanisms used by neurotrophic factors to promote axon growth in the mature, injured central nervous system are not well understood. Here we investigated the signaling cascades that control fibroblast growth factor‐2 (FGF‐2)‐mediated retinal ganglion cell (RGC) axon extension in vivo. For this purpose, a novel adeno‐associated virus (AAV) was used to deliver the FGF‐2 gene to RGCs, providing a sustained source of this neurotrophic factor. FGF‐2 gene transfer led to an approximately ten‐fold increase in the number of axons that extended past the lesion site compared with control nerves. Axon growth correlated with FGF‐2‐induced activation of the extracellular signal‐regulated kinases 1/2 (Erk1/2), but not phosphoinositide 3‐kinase or protein kinase C. Pharmacological inhibition of Erk1/2 activation resulted in an ∼80% decrease in the number of axons that regenerated in the injured optic nerve. Our data demonstrate that the Erk1/2 pathway is an essential signaling component in FGF‐2‐mediated axon regeneration in the mature, injured visual system. © 2006 Wiley‐Liss, Inc.