Dual-Specificity Phosphatase 14 Regulates Zebrafish Hair Cell Formation Through Activation of p38 Signaling Pathway

Guanyun,Wei1; Xu,Zhang1,2; Chengyun,Cai1; Jiajing,Sheng1; Mengting,Xu1; Cheng,Wang1; Qiuxiang,Gu1; Chao,Guo1; Fangyi,Chen3,4; Dong,Liu1; Fuping,Qian1

2022-03-23

10.3389/fncel.2022.840143

Frontiers in Cellular Neuroscience   影响因子和分区

1662-5102

1662-5102

Most cases of acquired hearing loss are due to degeneration and subsequent loss of cochlear hair cells. Whereas mammalian hair cells are not replaced when lost, in zebrafish, they constantly renew and regenerate after injury. However, the molecular mechanism among this difference remains unknown. Dual-specificity phosphatase 14 (DUSP14) is an important negative modulator of mitogen-activated protein kinase (MAPK) signaling pathways. Our study was to investigate the effects of DUSP14 on supporting cell development and hair cell regeneration and explore the potential mechanism. Our results showed that dusp14 gene is highly expressed in zebrafish developing neuromasts and otic vesicles. Behavior analysis showed that dusp14 deficiency resulted in hearing defects in zebrafish larvae, which were reversed by dusp14 mRNA treatment. Moreover, knockdown of dusp14 gene caused a significant decrease in the number of neuromasts and hair cells in both neuromast and otic vesicle, mainly due to the inhibition of the proliferation of supporting cells, which results in a decrease in the number of supporting cells and ultimately in the regeneration of hair cells. We further found significant changes in a series of MAPK pathway genes through transcriptome sequencing analysis of dusp14-deficient zebrafish, especially mapk12b gene in p38 signaling. Additionally, inhibiting p38 signaling effectively rescued all phenotypes caused by dusp14 deficiency, including hair cell and supporting cell reduction. These results suggest that DUSP14 might be a key gene to regulate supporting cell development and hair cell regeneration and is a potential target for the treatment of hearing loss.

DUSP14 supporting cell hair cell zebrafish proliferation regeneration

SCI

英语

通讯

National Natural Science Foundation of China[82001417] ; Natural Science Foundation of Jiangsu Province["BK20190920","BK20180048","BK20200966"]

Neurosciences & Neurology

Neurosciences

WOS:000780191900001

Frontiers Media SA

人工提交

1.Key Laboratory of Neuroregeneration of MOE, Nantong Laboratory of Development and Diseases, School of Life Sciences, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
2.Translational Medical Research Center, Wuxi No. 2 People’s Hospital, Affiliated Wuxi Clinical College of Nantong University, Wuxi, China
3.Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, China
4.Department of Biology, Brain Research Center, Southern University of Science and Technology, Shenzhen, China

Guanyun,Wei,Xu,Zhang,Chengyun,Cai,et al. Dual-Specificity Phosphatase 14 Regulates Zebrafish Hair Cell Formation Through Activation of p38 Signaling Pathway[J]. Frontiers in Cellular Neuroscience,2022,16.

Guanyun,Wei.,Xu,Zhang.,Chengyun,Cai.,Jiajing,Sheng.,Mengting,Xu.,...&Fuping,Qian.(2022).Dual-Specificity Phosphatase 14 Regulates Zebrafish Hair Cell Formation Through Activation of p38 Signaling Pathway.Frontiers in Cellular Neuroscience,16.

Guanyun,Wei,et al."Dual-Specificity Phosphatase 14 Regulates Zebrafish Hair Cell Formation Through Activation of p38 Signaling Pathway".Frontiers in Cellular Neuroscience 16(2022).