Sustained axon regeneration induced by co-deletion of PTEN and SOCS3
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Author(s)
Wang, Dongqing
Feng, Guoping
Sun, Fang
Park, Kevin K.
Belin, Stephane
Lu, Tao
Zhang, Kang
Yeung, Cecil
Yankner, Bruce A.
He, Zhigang
Date Issued
November 2011
Journal
Nature
Publisher
Nature Publishing Group
Citation
Sun, Fang et al. “Sustained Axon Regeneration Induced by Co-deletion of PTEN and SOCS3.” Nature 480.7377 (2011): 372–375.
Version
Author's final manuscript
Abstract
A formidable challenge in neural repair in the adult central nervous system (CNS) is the long distances that regenerating axons often need to travel in order to reconnect with their targets. Thus, a sustained capacity for axon regeneration is critical for achieving functional restoration. Although deletion of either phosphatase and tensin homologue (PTEN), a negative regulator of mammalian target of rapamycin (mTOR), or suppressor of cytokine signalling 3 (SOCS3), a negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, in adult retinal ganglion cells (RGCs) individually promoted significant optic nerve regeneration, such regrowth tapered off around 2 weeks after the crush injury. Here we show that, remarkably, simultaneous deletion of both PTEN and SOCS3 enables robust and sustained axon regeneration. We further show that PTEN and SOCS3 regulate two independent pathways that act synergistically to promote enhanced axon regeneration. Gene expression analyses suggest that double deletion not only results in the induction of many growth-related genes, but also allows RGCs to maintain the expression of a repertoire of genes at the physiological level after injury. Our results reveal concurrent activation of mTOR and STAT3 pathways as key for sustaining long-distance axon regeneration in adult CNS, a crucial step towards functional recovery.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
McGovern Institute for Brain Research at MIT
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DOI of Published Version
https://doi.org/10.1038/nature10594
