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Spinal axon regeneration evoked by replacing two growth cone proteins in adult neurons

Abstract

In contrast to peripheral nerves, damaged axons in the mammalian brain and spinal cord rarely regenerate. Peripheral nerve injury stimulates neuronal expression of many genes that are not generally induced by CNS lesions, but it is not known which of these genes are required for regeneration. Here we show that co-expressing two major growth cone proteins, GAP-43 and CAP-23, can elicit long axon extension by adult dorsal root ganglion (DRG) neurons in vitro. Moreover, this expression triggers a 60-fold increase in regeneration of DRG axons in adult mice after spinal cord injury in vivo. Replacing key growth cone components, therefore, could be an effective way to stimulate regeneration of CNS axons.

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Figure 1: GAP-43 and CAP-23 increase the propensity of adult neurons for axon growth in vitro.
Figure 2: Combined expression of GAP-43 and CAP-23 triggers an elongating mode of axon extension.
Figure 3: Stepwise induction of axon elongation by GAP-43 and CAP-23.
Figure 4: Expression of GAP-43 and CAP-23 and regeneration of spinal axons by large mechanosensory DRG neurons of transgenic mice in vivo.
Figure 5: Replacement of GAP-43 and CAP-23 permits regeneration of spinal sensory axons in vivo.

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Acknowledgements

We thank R. Chesebro for technical support, N. Cant for advice and assistance with retrograde labeling and L. Katz and J. Crowley for help with the fluorescence imaging. We also thank B. Finch, L. Katz, D. Purves, D. Chikaraishi, M. Nicolelis and A. Udvadia for comments on the manuscript. Support for this work was provided by the National Eye Institute (NIH), Novartis Pharmaceuticals and the Christopher Reeves Paralysis Foundation. K.R.B. is the recipient of a Ruth K. Broad Foundation fellowship.

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Correspondence to J. H. Pate Skene.

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Bomze, H., Bulsara, K., Iskandar, B. et al. Spinal axon regeneration evoked by replacing two growth cone proteins in adult neurons. Nat Neurosci 4, 38–43 (2001). https://doi.org/10.1038/82881

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