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Nature DOI:10.1038/nature10594

Sustained axon regeneration induced by co-deletion of PTEN and SOCS3.

Publication TypeJournal Article
Year of Publication2011
AuthorsSun, F, Park, KK, Belin, S, Wang, D, Lu, T, Chen, G, Zhang, K, Yeung, C, Feng, G, Yankner, BA, He, Z
Date Published2011 Nov 06
KeywordsAnimals, Axons, Cell Growth Processes, Gene Expression Regulation, Mice, Mice, Inbred C57BL, Nerve Crush, Nerve Regeneration, Optic Nerve, Optic Nerve Injuries, PTEN Phosphohydrolase, Retinal Ganglion Cells, Signal Transduction, STAT3 Transcription Factor, Suppressor of Cytokine Signaling 3 Protein, Suppressor of Cytokine Signaling Proteins

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.


Alternate JournalNature
PubMed ID22056987
PubMed Central IDPMC3240702
Grant ListR01 EY021526 / EY / NEI NIH HHS / United States
R01 EY021374 / EY / NEI NIH HHS / United States
R01 EY021526-01 / EY / NEI NIH HHS / United States
R01 EY021342-01A1 / EY / NEI NIH HHS / United States
DP1 AG044161 / AG / NIA NIH HHS / United States
R01 EY021342 / EY / NEI NIH HHS / United States
R01 EY018660 / EY / NEI NIH HHS / United States