PUBLICATION

Grhl1 deficiency affects inner ear development in zebrafish

Authors

Liu, F., Yang, F., Wen, D., Xia, W., Hao, L., Hu, J., Zong, J., Shen, X., Ma, J., Jiang, N., Sun, S., Zhang, J., Wang, H., Wang, X., Ma, Z., Ma, D.

ID

ZDB-PUB-150422-3

Date

2015

Source

The International journal of developmental biology 59(10-11-12): 417-423 (Journal)

Registered Authors

Wang, Xu, Yang, Fan

Keywords

GRHL1, zebrafish, desmosom, hair cell, DSG1

MeSH Terms

Apoptosis*
Real-Time Polymerase Chain Reaction
Hair Cells, Auditory/cytology*
Hair Cells, Auditory/metabolism
Organogenesis
Animals
Repressor Proteins/deficiency*
Repressor Proteins/genetics
Embryo, Nonmammalian/cytology
Embryo, Nonmammalian/metabolism
Zebrafish/embryology*
Zebrafish/genetics
Zebrafish/metabolism
Reverse Transcriptase Polymerase Chain Reaction
Zebrafish Proteins/deficiency*
Zebrafish Proteins/genetics
Immunoenzyme Techniques
Gene Expression Regulation, Developmental
RNA, Messenger/genetics
Desmosomes
Ear, Inner/embryology
Ear, Inner/growth & development*
Ear, Inner/pathology
Blotting, Western

(all 24)

PubMed

25896282 Full text @ Int. J. Dev. Biol.

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.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
grhl1	AB	standard conditions	Prim-5	olfactory placode	ISH	Fig. 1
grhl1	AB	standard conditions	Prim-5	otic vesicle	ISH	Fig. 1
grhl1	AB	standard conditions	Prim-5	posterior lateral line primordium	ISH	Fig. 1
grhl1	AB	standard conditions	Prim-5	pronephric duct	ISH	Fig. 1
grhl1	AB	standard conditions	Shield to Day 4	whole organism	RTPCR	Fig. 1
grhl1	AB	standard conditions	5-9 somites	whole organism	ISH	Fig. 1

1 - 6 of 6

Show

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB + MO1-grhl1	standard conditions	Pec-fin	neuromast hair cell decreased amount, abnormal	Fig. 2
AB + MO1-grhl1	standard conditions	Pec-fin	otolith amount, abnormal	Fig. 2
AB + MO1-grhl1	standard conditions	Pec-fin	otolith decreased size, abnormal	Fig. 2
AB + MO1-grhl1	standard conditions	Pec-fin	otolith mislocalised, abnormal	Fig. 2
AB + MO1-grhl1	standard conditions	Pec-fin	semicircular canal malformed, abnormal	Fig. 2
AB + MO1-grhl1	standard conditions	Day 5	hair cell apoptotic process increased occurrence, abnormal	Fig. 3
AB + MO1-grhl1	standard conditions	Day 5	neuromast hair cell apoptotic, abnormal	Fig. 3
AB + MO1-grhl1	standard conditions	Day 5	neuromast hair cell desmosome damaged, abnormal	Fig. 3
AB + MO1-grhl1	standard conditions	Day 5	neuromast hair cell desmosome disorganized, abnormal	Fig. 4
AB + MO1-grhl1	standard conditions	Day 5	sensory perception of sound disrupted, abnormal	Fig. 4

1 - 10 of 11

Show

Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
s356tTg	Tg(pou4f3:GAP-GFP)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
grhl1	MO1-grhl1	MRPHLNO
tp53	MO4-tp53	MRPHLNO

Fish

Fish
AB
AB + MO1-grhl1

Antibodies

Orthology

Gene	Orthology
grhl1
grhl2b
grhl3

Engineered Foreign Genes

Marker	Marker Type	Name
GFP	EFG	GFP

Mapping

Liu et al., 2015 ZDB-PUB-150422-3 PMID:25896282

Grhl1 deficiency affects inner ear development in zebrafish

Liu et al., 2015

ZDB-PUB-150422-3
PMID:25896282