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

Fang Sun, Kevin Park, Stephane Belin, Dongqing Wang, Tao Lu, Gang Chen, Kang Zhang, Cecil Yeung, Guoping Feng, Bruce A. Yankner, Zhigang He

Research output: Contribution to journalArticle

347 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)372-375
Number of pages4
JournalNature
Volume480
Issue number7377
DOIs
StatePublished - Dec 15 2011

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Phosphoric Monoester Hydrolases
Axons
Regeneration
Cytokines
Retinal Ganglion Cells
Sirolimus
Central Nervous System
Janus Kinases
Nerve Regeneration
Optic Nerve
Transducers
Genes
Tensins
Gene Expression
Wounds and Injuries
Growth

ASJC Scopus subject areas

  • General

Cite this

Sun, F., Park, K., Belin, S., Wang, D., Lu, T., Chen, G., ... He, Z. (2011). Sustained axon regeneration induced by co-deletion of PTEN and SOCS3. Nature, 480(7377), 372-375. https://doi.org/10.1038/nature10594

Sustained axon regeneration induced by co-deletion of PTEN and SOCS3. / Sun, Fang; Park, Kevin; Belin, Stephane; Wang, Dongqing; Lu, Tao; Chen, Gang; Zhang, Kang; Yeung, Cecil; Feng, Guoping; Yankner, Bruce A.; He, Zhigang.

In: Nature, Vol. 480, No. 7377, 15.12.2011, p. 372-375.

Research output: Contribution to journalArticle

Sun, F, Park, K, Belin, S, Wang, D, Lu, T, Chen, G, Zhang, K, Yeung, C, Feng, G, Yankner, BA & He, Z 2011, 'Sustained axon regeneration induced by co-deletion of PTEN and SOCS3', Nature, vol. 480, no. 7377, pp. 372-375. https://doi.org/10.1038/nature10594
Sun F, Park K, Belin S, Wang D, Lu T, Chen G et al. Sustained axon regeneration induced by co-deletion of PTEN and SOCS3. Nature. 2011 Dec 15;480(7377):372-375. https://doi.org/10.1038/nature10594
Sun, Fang ; Park, Kevin ; Belin, Stephane ; Wang, Dongqing ; Lu, Tao ; Chen, Gang ; Zhang, Kang ; Yeung, Cecil ; Feng, Guoping ; Yankner, Bruce A. ; He, Zhigang. / Sustained axon regeneration induced by co-deletion of PTEN and SOCS3. In: Nature. 2011 ; Vol. 480, No. 7377. pp. 372-375.
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