title: Grhl1 deficiency affects inner ear development in zebrafish.
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.
authors.affiliation: Key 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, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Danping
authors.initials: D
authors.lastname: Wen
authors.forename: Wenjun
authors.initials: W
authors.lastname: Xia
authors.forename: Lili
authors.initials: L
authors.lastname: Hao
authors.forename: JiongJiong
authors.initials: J
authors.lastname: Hu
authors.forename: Jie
authors.initials: J
authors.lastname: Zong
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Shen
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.forename: Shaoyang
authors.initials: S
authors.lastname: Sun
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Huijun
authors.initials: H
authors.lastname: Wang
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Zhaoxin
authors.initials: Z
authors.lastname: Ma
authors.forename: Duan
authors.initials: D
authors.lastname: Ma
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D003896:Desmosomes; D007758:Ear, Inner / Q000196:embryology / Q000254:growth & development* / Q000473:pathology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006198:Hair Cells, Auditory / Q000166:cytology* / Q000378:metabolism; D007124:Immunoenzyme Techniques; D038081:Organogenesis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000172:deficiency* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000172:deficiency* / Q000235:genetics
chemical_list: C518352:GRHL1 protein, human; D012333:RNA, Messenger; D012097:Repressor Proteins; D029961:Zebrafish Proteins