An Intrinsic Epigenetic Barrier for Functional Axon Regeneration

Research output: Contribution to journalArticle

Yi-Lan Weng, Ran An, Jessica Cassin, Jessica Joseph, Ruifa Mi, Chen Wang, Chun Zhong, Seung-Gi Jin, Gerd P Pfeifer, Alfonso Bellacosa, Xinzhong Dong, Ahmet Hoke, Zhigang He, Hongjun Song, Guo-Li Ming

Mature neurons in the adult peripheral nervous system can effectively switch from a dormant state with little axonal growth to robust axon regeneration upon injury. The mechanisms by which injury unlocks mature neurons' intrinsic axonal growth competence are not well understood. Here, we show that peripheral sciatic nerve lesion in adult mice leads to elevated levels of Tet3 and 5-hydroxylmethylcytosine in dorsal root ganglion (DRG) neurons. Functionally, Tet3 is required for robust axon regeneration of DRG neurons and behavioral recovery. Mechanistically, peripheral nerve injury induces DNA demethylation and upregulation of multiple regeneration-associated genes in a Tet3- and thymine DNA glycosylase-dependent fashion in DRG neurons. In addition, Pten deletion-induced axon regeneration of retinal ganglion neurons in the adult CNS is attenuated upon Tet1 knockdown. Together, our study suggests an epigenetic barrier that can be removed by active DNA demethylation to permit axon regeneration in the adult mammalian nervous system.

Original languageEnglish (US)
Pages (from-to)337-346.e6
JournalNeuron
Volume94
Issue number2
DOIs
StatePublished - Apr 19 2017

PMID: 28426967

PMCID: PMC6007997

Altmetrics

Cite this

Standard

An Intrinsic Epigenetic Barrier for Functional Axon Regeneration. / Weng, Yi-Lan; An, Ran; Cassin, Jessica; Joseph, Jessica; Mi, Ruifa; Wang, Chen; Zhong, Chun; Jin, Seung-Gi; Pfeifer, Gerd P; Bellacosa, Alfonso; Dong, Xinzhong; Hoke, Ahmet; He, Zhigang; Song, Hongjun; Ming, Guo-Li.

In: Neuron, Vol. 94, No. 2, 19.04.2017, p. 337-346.e6.

Research output: Contribution to journalArticle

Harvard

Weng, Y-L, An, R, Cassin, J, Joseph, J, Mi, R, Wang, C, Zhong, C, Jin, S-G, Pfeifer, GP, Bellacosa, A, Dong, X, Hoke, A, He, Z, Song, H & Ming, G-L 2017, 'An Intrinsic Epigenetic Barrier for Functional Axon Regeneration' Neuron, vol. 94, no. 2, pp. 337-346.e6. https://doi.org/10.1016/j.neuron.2017.03.034

APA

Weng, Y-L., An, R., Cassin, J., Joseph, J., Mi, R., Wang, C., ... Ming, G-L. (2017). An Intrinsic Epigenetic Barrier for Functional Axon Regeneration. Neuron, 94(2), 337-346.e6. https://doi.org/10.1016/j.neuron.2017.03.034

Vancouver

Weng Y-L, An R, Cassin J, Joseph J, Mi R, Wang C et al. An Intrinsic Epigenetic Barrier for Functional Axon Regeneration. Neuron. 2017 Apr 19;94(2):337-346.e6. https://doi.org/10.1016/j.neuron.2017.03.034

Author

Weng, Yi-Lan ; An, Ran ; Cassin, Jessica ; Joseph, Jessica ; Mi, Ruifa ; Wang, Chen ; Zhong, Chun ; Jin, Seung-Gi ; Pfeifer, Gerd P ; Bellacosa, Alfonso ; Dong, Xinzhong ; Hoke, Ahmet ; He, Zhigang ; Song, Hongjun ; Ming, Guo-Li. / An Intrinsic Epigenetic Barrier for Functional Axon Regeneration. In: Neuron. 2017 ; Vol. 94, No. 2. pp. 337-346.e6.

BibTeX

@article{a5fd415e22934045b8c74cf6b6258b2c,
title = "An Intrinsic Epigenetic Barrier for Functional Axon Regeneration",
abstract = "Mature neurons in the adult peripheral nervous system can effectively switch from a dormant state with little axonal growth to robust axon regeneration upon injury. The mechanisms by which injury unlocks mature neurons' intrinsic axonal growth competence are not well understood. Here, we show that peripheral sciatic nerve lesion in adult mice leads to elevated levels of Tet3 and 5-hydroxylmethylcytosine in dorsal root ganglion (DRG) neurons. Functionally, Tet3 is required for robust axon regeneration of DRG neurons and behavioral recovery. Mechanistically, peripheral nerve injury induces DNA demethylation and upregulation of multiple regeneration-associated genes in a Tet3- and thymine DNA glycosylase-dependent fashion in DRG neurons. In addition, Pten deletion-induced axon regeneration of retinal ganglion neurons in the adult CNS is attenuated upon Tet1 knockdown. Together, our study suggests an epigenetic barrier that can be removed by active DNA demethylation to permit axon regeneration in the adult mammalian nervous system.",
keywords = "5-Methylcytosine/analogs & derivatives, Animals, Axons/metabolism, Epigenesis, Genetic/drug effects, Ganglia, Spinal/cytology, Mice, Inbred C57BL, Nerve Regeneration/drug effects, Peripheral Nerve Injuries/drug therapy",
author = "Yi-Lan Weng and Ran An and Jessica Cassin and Jessica Joseph and Ruifa Mi and Chen Wang and Chun Zhong and Seung-Gi Jin and Pfeifer, {Gerd P} and Alfonso Bellacosa and Xinzhong Dong and Ahmet Hoke and Zhigang He and Hongjun Song and Guo-Li Ming",
note = "Copyright {\circledC} 2017 Elsevier Inc. All rights reserved.",
year = "2017",
month = "4",
day = "19",
doi = "10.1016/j.neuron.2017.03.034",
language = "English (US)",
volume = "94",
pages = "337--346.e6",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "2",

}

RIS

TY - JOUR

T1 - An Intrinsic Epigenetic Barrier for Functional Axon Regeneration

AU - Weng, Yi-Lan

AU - An, Ran

AU - Cassin, Jessica

AU - Joseph, Jessica

AU - Mi, Ruifa

AU - Wang, Chen

AU - Zhong, Chun

AU - Jin, Seung-Gi

AU - Pfeifer, Gerd P

AU - Bellacosa, Alfonso

AU - Dong, Xinzhong

AU - Hoke, Ahmet

AU - He, Zhigang

AU - Song, Hongjun

AU - Ming, Guo-Li

N1 - Copyright © 2017 Elsevier Inc. All rights reserved.

PY - 2017/4/19

Y1 - 2017/4/19

N2 - Mature neurons in the adult peripheral nervous system can effectively switch from a dormant state with little axonal growth to robust axon regeneration upon injury. The mechanisms by which injury unlocks mature neurons' intrinsic axonal growth competence are not well understood. Here, we show that peripheral sciatic nerve lesion in adult mice leads to elevated levels of Tet3 and 5-hydroxylmethylcytosine in dorsal root ganglion (DRG) neurons. Functionally, Tet3 is required for robust axon regeneration of DRG neurons and behavioral recovery. Mechanistically, peripheral nerve injury induces DNA demethylation and upregulation of multiple regeneration-associated genes in a Tet3- and thymine DNA glycosylase-dependent fashion in DRG neurons. In addition, Pten deletion-induced axon regeneration of retinal ganglion neurons in the adult CNS is attenuated upon Tet1 knockdown. Together, our study suggests an epigenetic barrier that can be removed by active DNA demethylation to permit axon regeneration in the adult mammalian nervous system.

AB - Mature neurons in the adult peripheral nervous system can effectively switch from a dormant state with little axonal growth to robust axon regeneration upon injury. The mechanisms by which injury unlocks mature neurons' intrinsic axonal growth competence are not well understood. Here, we show that peripheral sciatic nerve lesion in adult mice leads to elevated levels of Tet3 and 5-hydroxylmethylcytosine in dorsal root ganglion (DRG) neurons. Functionally, Tet3 is required for robust axon regeneration of DRG neurons and behavioral recovery. Mechanistically, peripheral nerve injury induces DNA demethylation and upregulation of multiple regeneration-associated genes in a Tet3- and thymine DNA glycosylase-dependent fashion in DRG neurons. In addition, Pten deletion-induced axon regeneration of retinal ganglion neurons in the adult CNS is attenuated upon Tet1 knockdown. Together, our study suggests an epigenetic barrier that can be removed by active DNA demethylation to permit axon regeneration in the adult mammalian nervous system.

KW - 5-Methylcytosine/analogs & derivatives

KW - Animals

KW - Axons/metabolism

KW - Epigenesis, Genetic/drug effects

KW - Ganglia, Spinal/cytology

KW - Mice, Inbred C57BL

KW - Nerve Regeneration/drug effects

KW - Peripheral Nerve Injuries/drug therapy

U2 - 10.1016/j.neuron.2017.03.034

DO - 10.1016/j.neuron.2017.03.034

M3 - Article

VL - 94

SP - 337-346.e6

JO - Neuron

T2 - Neuron

JF - Neuron

SN - 0896-6273

IS - 2

ER -

ID: 41875401