title: Ildr1b is essential for semicircular canal development, migration of the posterior lateral line primordium and hearing ability in zebrafish: implications for a role in the recessive hearing impairment DFNB42.
abstract: Immunoglobulin-like domain containing receptor 1 (ILDR1) is a poorly characterized gene that was first identified in lymphoma cells. Recently, ILDR1 has been found to be responsible for autosomal recessive hearing impairment DFNB42. Patients with ILDR1 mutations cause bilateral non-progressive moderate-to-profound sensorineural hearing impairment. However, the etiology and mechanism of ILDR1-related hearing loss remains to be elucidated. In order to uncover the pathology of DFNB42 deafness, we used the morpholino injection technique to establish an ildr1b-morphant zebrafish model. Ildr1b-morphant zebrafish displayed defective hearing and imbalanced swimming, and developmental delays were seen in the semicircular canals of the inner ear. The gene expression profile and real-time PCR revealed down-regulation of atp1b2b (encoding Na(+)/K(+) transporting, beta 2b polypeptide) in ildr1b-morphant zebrafish. We found that injection of atp1b2b mRNA into ildr1b-knockdown zebrafish could rescue the phenotype of developmental delay of the semicircular canals. Moreover, ildr1b-morphant zebrafish had reduced numbers of lateral line neuromasts due to the disruption of lateral line primordium migration. In situ hybridization showed the involvement of attenuated FGF signaling and the chemokine receptor 4b (cxcr4b) and chemokine receptor 7b (cxcr7b) in posterior lateral line primordium of ildr1b-morphant zebrafish. We concluded that Ildr1b is crucial for the development of the inner ear and the lateral line system. This study provides the first evidence for the mechanism of Ildr1b on hearing in vivo and sheds light on the pathology of DFNB42.
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200032, PR China, Institutes of Biomedical Sciences, Fudan University, No 138 Yixueyuan Road, Shanghai 200032, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Sang
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, No 138 Yixueyuan Road, Shanghai 200032, PR China.
authors.forename: Junyu
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, No 138 Yixueyuan Road, Shanghai 200032, PR China.
authors.forename: Ruizhi
authors.initials: R
authors.lastname: Feng
authors.affiliation: The Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, No 138 Yixueyuan Road, Shanghai 200032, PR China.
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, No 138 Yixueyuan Road, Shanghai 200032, PR China.
authors.forename: Xinzhi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, No 138 Yixueyuan Road, Shanghai 200032, PR China.
authors.forename: Qinghe
authors.initials: Q
authors.lastname: Xing
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China.
authors.forename: Weiyu
authors.initials: W
authors.lastname: Chen
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China.
authors.forename: Jiulin
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Otolaryngology, Eye and ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, PR China.
authors.forename: Shan
authors.initials: S
authors.lastname: Sun
authors.affiliation: Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210096, China and.
authors.forename: Renjie
authors.initials: R
authors.lastname: Chai
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong 226001, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200032, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, No 138 Yixueyuan Road, Shanghai 200032, PR China, Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200030, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Otolaryngology, Eye and ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, PR China, wangleiwanglei@fudan.edu.cn hwli@shmu.edu.cn.
authors.forename: Huawei
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200032, PR China, Institutes of Biomedical Sciences, Fudan University, No 138 Yixueyuan Road, Shanghai 200032, PR China, wangleiwanglei@fudan.edu.cn hwli@shmu.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D007758:Ear, Inner / Q000196:embryology / Q000378:metabolism; D006309:Hearing / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000196:embryology; D053403:Lateral Line System / Q000196:embryology / Q000378:metabolism; D023421:Models, Animal; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D012665:Semicircular Canals / Q000196:embryology* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C000602348:Ildr1b protein, zebrafish; D011956:Receptors, Cell Surface; D029961:Zebrafish Proteins