Polycomb protein family member CBX7 regulates intrinsic axon growth and regeneration

Run-Shan Duan; Gang-Bin Tang; Hong-Zhen Du; Yi-Wen Hu; Pei-Pei Liu; Ya-Jie Xu; Yu-Qiang Zeng; Shuang-Feng Zhang; Rui-Ying Wang; Zhao-Qian Teng; Chang-Mei Liu

doi:10.1038/s41418-018-0064-0

Polycomb protein family member CBX7 regulates intrinsic axon growth and regeneration

Cell Death Differ. 2018 Sep;25(9):1598-1611. doi: 10.1038/s41418-018-0064-0. Epub 2018 Feb 19.

Authors

Run-Shan Duan^#¹, Gang-Bin Tang^#¹, Hong-Zhen Du^#¹, Yi-Wen Hu², Pei-Pei Liu^{1

3}, Ya-Jie Xu^{1

3}, Yu-Qiang Zeng¹, Shuang-Feng Zhang^{1

4}, Rui-Ying Wang², Zhao-Qian Teng^{1

3}, Chang-Mei Liu^{5

6}

Affiliations

¹ State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
² Department of Orthopaedic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, 541001, China.
³ University of Chinese Academy of Sciences, Beijing, 100049, China.
⁴ School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China.
⁵ State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [email protected].
⁶ University of Chinese Academy of Sciences, Beijing, 100049, China. [email protected].

^# Contributed equally.

Abstract

Neurons in the central nervous system (CNS) lose their intrinsic ability and fail to regenerate, but the underlying mechanisms are largely unknown. Polycomb group (PcG) proteins, which include PRC1 and PRC2 complexes function as gene repressors and are involved in many biological processes. Here we report that PRC1 components (polycomb chromobox (CBX) 2, 7, and 8) are novel regulators of axon growth and regeneration. Especially, knockdown of CBX7 in either embryonic cortical neurons or adult dorsal root ganglion (DRG) neurons enhances their axon growth ability. Two important transcription factors GATA4 and SOX11 are functional downstream targets of CBX7 in controlling axon regeneration. Moreover, knockdown of GATA4 or SOX11 in cultured DRG neurons inhibits axon regeneration response from CBX7 downregulation in DRG neurons. These findings suggest that targeting CBX signaling pathway may be a novel approach for promoting the intrinsic regenerative capacity of damaged CNS neurons.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Axons / physiology*
Cells, Cultured
Down-Regulation
GATA4 Transcription Factor / antagonists & inhibitors
GATA4 Transcription Factor / genetics
GATA4 Transcription Factor / metabolism
Ganglia, Spinal / cytology
Mice
Neurons / cytology
Neurons / metabolism
Polycomb Repressive Complex 1 / antagonists & inhibitors
Polycomb Repressive Complex 1 / genetics
Polycomb Repressive Complex 1 / metabolism
Polycomb-Group Proteins / antagonists & inhibitors
Polycomb-Group Proteins / genetics
Polycomb-Group Proteins / metabolism*
RNA Interference
RNA, Small Interfering / metabolism
Regeneration
SOXC Transcription Factors / antagonists & inhibitors
SOXC Transcription Factors / genetics
SOXC Transcription Factors / metabolism
Sciatic Nerve / injuries

Substances

Cbx7 protein, mouse
GATA4 Transcription Factor
Gata4 protein, mouse
Polycomb-Group Proteins
RNA, Small Interfering
SOXC Transcription Factors
Sox11 protein, mouse
Polycomb Repressive Complex 1