Sustained axon regeneration induced by co-deletion of PTEN and SOCS3
Author(s)
Wang, Dongqing; Feng, Guoping; Sun, Fang; Park, Kevin K.; Belin, Stephane; Lu, Tao; Zhang, Kang; Yeung, Cecil; Yankner, Bruce A.; He, Zhigang; ... Show more Show less
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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.
Date issued
2011-11Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; McGovern Institute for Brain Research at MITJournal
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
ISSN
1745-8382
1745-8390