The Role of FoxG1 in the Inner Ear.

Yanyan Ding,Renjie Chai,Zuhong He,Weijia Kong,Wei Meng

doi:10.3389/fcell.2020.614954

Abstract

Sensorineural deafness is mainly caused by damage to the tissues of the inner ear, and hearing impairment has become an increasingly serious global health problem. When the inner ear is abnormally developed or is damaged by inflammation, ototoxic drugs, or blood supply disorders, auditory signal transmission is inhibited resulting in hearing loss. Forkhead box G1 (FoxG1) is an important nuclear transcriptional regulator, which is related to the differentiation, proliferation, development, and survival of cells in the brain, telencephalon, inner ear, and other tissues. Previous studies have shown that when FoxG1 is abnormally expressed, the development and function of inner ear hair cells is impaired. This review discusses the role and regulatory mechanism of FoxG1 in inner ear tissue from various aspects – such as the effect on inner ear development, the maintenance of inner ear structure and function, and its role in the inner ear when subjected to various stimulations or injuries – in order to explain the potential significance of FoxG1 as a new target for the treatment of hearing loss.

Highlights

The number of people suffering from hearing impairment in the world was approximately 500 million in 2015, ranking fourth among all disability factors and ahead of diabetes and dementia (GBD, 2016)
Through EDU assay and in vitro sphereforming assay, we found that this phenotype was mainly due to the knockout of Foxg1 promoting the trans-differentiation of supporting cells to hair cells (HCs), and the expression of genes related to the cell cycle and Notch signaling pathway was affected (Zhang et al, 2020)
Forkhead box G1 plays a key role in the development of the cerebral cortex and neurons, and has a close regulatory relationship with the development of the inner ear, the survival of HCs, and the protection of HCs against injury

Summary

INTRODUCTION

The number of people suffering from hearing impairment in the world was approximately 500 million in 2015, ranking fourth among all disability factors and ahead of diabetes and dementia (GBD, 2016). After conditional knockout Foxg in the HCs, we found that the number of HCs in the apex turn of the cochlea of newborn mice increased significantly, indicating that the deletion of Foxg expression caused the disorder of HC proliferation and differentiation (He et al, 2019). The above findings indicated that FoxG1 can affect the differentiation and proliferation of inner ear NPCs through the regulation of multiple signal pathways and related factors expression. It is speculated that this phenomenon is due to the body promotes the survival of auditory neurons in the inner ear through activating the expression of Foxg, thereby reducing the cochlea development abnormal caused by the deletion of C-Raf expression. We found that in D-galactoseinduced aging HCs, FoxG1 inhibits the increase in ROS in cells induced by LPS by activating autophagy, thereby regulating the sensitivity of aging HCs to inflammation and maintaining the function and survival of HCs (He et al, 2020a; Figure 2)

DISCUSSION

CONCLUSION