Polycomb protein family member CBX7 regulates intrinsic axon growth and regeneration

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

doi:10.1038/s41418-018-0064-0

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.

Highlights

Injured mature peripheral neurons successfully activate an array of regeneration-associated genes that enhance the intrinsic growth capacity to enable axon regeneration [1, 2]
With electroporation of a group of three different small interfering RNAs (siRNAs) that were designed to minimize the off-target effects (ON-TARGET plus, Shanghai GenePharma Co., Ltd), we found that acute downregulation of SOX11 resulted in impaired regenerative axon growth of adult dorsal root ganglion (DRG) neurons (Fig. 7b–d), which was consistent with published findings [30, 31]
This study demonstrates that CBX family members have differential expressions during the cortical development and response differently to sciatic nerve injury

Summary

Introduction

Injured mature peripheral neurons successfully activate an array of regeneration-associated genes that enhance the intrinsic growth capacity to enable axon regeneration [1, 2]. Axons within the central nervous system (CNS). Epigenetic regulation, including DNA methylation, histone modification, and non-coding RNAs, is emerging to be a key cellular mechanism to control gene expression [6]. Several recent studies have explored the roles of epigenetic modifications such as histone acetylation and non-coding RNAs in axon regeneration. The other epigenetic mechanisms such as histone acetylation and non-coding RNAs have pivotal roles in determining the regenerative capacity in neurons [1, 10]

Methods

Results

Conclusion