Sustained axon regeneration induced by co-deletion of pten and socs3

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 injury1,2.

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. Access through your institution Buy or subscribe This is a preview of subscription

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ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS ELK-1 REGULATES RETINAL GANGLION CELL

AXON REGENERATION AFTER INJURY Article Open access 19 October 2022 _MARCKS_ OVEREXPRESSION IN RETINAL GANGLION CELLS PROMOTES OPTIC NERVE REGENERATION Article Open access 18 December 2024

KNOCKDOWN OF PORF-2 RESTORES VISUAL FUNCTION AFTER OPTIC NERVE CRUSH INJURY Article Open access 28 August 2023 ACCESSION CODES DATA DEPOSITS Microarray data are deposited in Gene Expression

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Scholar  Download references ACKNOWLEDGEMENTS We thank M. Curry and C. Wang for technical support, H. Sasaki and F. Wang for providing Stat3f/f and Rosa-lox-STOP-lox-Tomato mice, J. Gray, M.

Hemberg, J. Choi, J. Ngai and W. Wang for advice on microarray and data analysis, and J. Gray, X. He, T. Schwarz, F. Wang, W. Wang and C. Woolf for reading the manuscript. This study was

supported by grants from Wings for Life (to F.S.), Miami Project to Cure Paralysis (to K.K.P.) and NEI (to Z.H.). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * and Department of Neurology,

F.M. Kirby Neurobiology Center, Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, 02115, Massachusetts, USA Fang Sun, Stephane Belin, Gang Chen, Cecil Yeung & 

Zhigang He * Department of Neurological Surgery, Miami Project to Cure Paralysis, Miller School of Medicine, University of Miami, Miami, 33136, Florida, USA Kevin K. Park * Department of

Brain and Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA Dongqing Wang & Guoping Feng * Department

of Genetics, Harvard Medical School, Boston, 02115, Massachusetts, USA Tao Lu & Bruce A. Yankner * Shiley Eye Center, University of California at San Diego, La Jolla, 92093, California,

USA Kang Zhang Authors * Fang Sun View author publications You can also search for this author inPubMed Google Scholar * Kevin K. Park View author publications You can also search for this

author inPubMed Google Scholar * Stephane Belin View author publications You can also search for this author inPubMed Google Scholar * Dongqing Wang View author publications You can also

search for this author inPubMed Google Scholar * Tao Lu View author publications You can also search for this author inPubMed Google Scholar * Gang Chen View author publications You can also

search for this author inPubMed Google Scholar * Kang Zhang View author publications You can also search for this author inPubMed Google Scholar * Cecil Yeung View author publications You

can also search for this author inPubMed Google Scholar * Guoping Feng View author publications You can also search for this author inPubMed Google Scholar * Bruce A. Yankner View author

publications You can also search for this author inPubMed Google Scholar * Zhigang He View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS F.S,

K.K.P., K.Z. and Z.H. conceived and F.S., K.K.P., S.B., G.C. and C.Y. performed the experiments. D.W. and G.F. provided YFP-17 mice, F.S., T.L., B.A.Y. and Z.H. analysed gene array data.

F.S., K.K.P. and Z.H. prepared the manuscript. CORRESPONDING AUTHOR Correspondence to Zhigang He. ETHICS DECLARATIONS COMPETING INTERESTS Z.H. is a co-founder of Axonis. SUPPLEMENTARY

INFORMATION SUPPLEMENTARY FIGURES The file contains Supplementary Figures 1-12 with legends. (PDF 2817 kb) POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1 POWERPOINT SLIDE FOR FIG. 2

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axon regeneration induced by co-deletion of PTEN and SOCS3. _Nature_ 480, 372–375 (2011). https://doi.org/10.1038/nature10594 Download citation * Received: 01 June 2011 * Accepted: 28

September 2011 * Published: 06 November 2011 * Issue Date: 15 December 2011 * DOI: https://doi.org/10.1038/nature10594 SHARE THIS ARTICLE Anyone you share the following link with will be

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