Int. J. Dev. Biol. 59: 417 - 423 (2015)
doi: 10.1387/ijdb.140230FL
© UPV/EHU Press

Grhl1 deficiency affects inner ear development in zebrafish

Fei Liu1, Fan Yang1, Danping Wen1, Wenjun Xia1, Lili Hao1, JiongJiong Hu2, Jie Zong3, Xiaofang Shen1, Jing Ma1, Nan Jiang1, Shaoyang Sun1, Jin Zhang1, Huijun Wang4, Xu Wang1, Zhaoxin Ma2 and Duan Ma*,1,4

1Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institute of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, 2Department of Otorhinolaryngology, Shanghai East Hospital, Tongji University, 3Novel bioinformatics Co., Ltd and 4Children's Hospital of Fudan University, Fudan University, Shanghai, China

ABSTRACT Many genes that have been found to contribute to deafness are currently being studied. Some 87 non-syndromic hereditary deafness genes have been confirmed. Proteins associated with cochlear development have also been confirmed. Some of these proteins have important relationships with gap junctions (GJ) and tight junctions (TJ). However, the desmosome junction has received little attention due to controversy over whether it could be detected in the inner ear. GRHL1 is a conserved transcriptional regulator, and it is key to vertebrate desmosome formation. GRHL2 has been confirmed as a deafness gene at the DFNA28 locus. These two homologous proteins have similar sequences and functions. Here, a grhl1 down-regulated zebrafish model exhibited inner ear developmental malformations, including missing otoliths, disordered and abnormal numbers of hair cells in the inner ear and lateral line, and sound insensitivity. The mutant zebrafish swam in circles. Hair cell apoptosis was evident. Under electron microscopy, desmosomes in the otic sensory epithelium were found to be damaged. These defects were partially rescued by treatment with either GRHL1 or its target gene, DSG1. Collectively, these data are the first to indicate that grhl1 is important to the developing inner ear epithelia in zebrafish and that it acts via desmosome junction regulation.

Keywords:

GRHL1, zebrafish, desmosom, hair cell, DSG1

*Corresponding author e-mail: duanma@fudan.edu.cn; mzhx114@163.com