title: Otolith tethering in the zebrafish otic vesicle requires Otogelin and α-Tectorin.
abstract: Otoliths are biomineralised structures important for balance and hearing in fish. Their counterparts in the mammalian inner ear, otoconia, have a primarily vestibular function. Otoliths and otoconia form over sensory maculae and are attached to the otolithic membrane, a gelatinous extracellular matrix that provides a physical coupling between the otolith and the underlying sensory epithelium. In this study, we have identified two proteins required for otolith tethering in the zebrafish ear, and propose that there are at least two stages to this process: seeding and maintenance. The initial seeding step, in which otolith precursor particles tether directly to the tips of hair cell kinocilia, fails to occur in the einstein (eis) mutant. The gene disrupted in eis is otogelin (otog); mutations in the human OTOG gene have recently been identified as causative for deafness and vestibular dysfunction (DFNB18B). At later larval stages, maintenance of otolith tethering to the saccular macula is dependent on tectorin alpha (tecta) function, which is disrupted in the rolling stones (rst) mutant. α-Tectorin (Tecta) is a major constituent of the tectorial membrane in the mammalian cochlea. Mutations in the human TECTA gene can cause either dominant (DFNA8/12) or recessive (DFNB21) forms of deafness. Our findings indicate that the composition of extracellular otic membranes is highly conserved between mammals and fish, reinforcing the view that the zebrafish is an excellent model system for the study of deafness and vestibular disease.
authors.affiliation: Bateson Centre and Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
authors.forename: Georgina A
authors.initials: GA
authors.lastname: Stooke-Vaughan
authors.affiliation: Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Nikolaus D
authors.initials: ND
authors.lastname: Obholzer
authors.affiliation: Bateson Centre and Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Baxendale
authors.affiliation: Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Sean G
authors.initials: SG
authors.lastname: Megason
authors.affiliation: Bateson Centre and Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK t.whitfield@sheffield.ac.uk.
authors.forename: Tanya T
authors.initials: TT
authors.lastname: Whitfield
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D003638:Deafness / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005453:Fluorescence; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D010037:Otolithic Membrane / Q000196:embryology* / Q000378:metabolism*; D010590:Phalloidine; D015837:Vestibular Diseases / Q000235:genetics*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016326:Extracellular Matrix Proteins; D008562:Membrane Glycoproteins; C000597691:Otog protein, zebrafish; C000597692:Tecta protein, zebrafish; D029961:Zebrafish Proteins; D010590:Phalloidine
keywords: Deafness; Otogelin; Otolith; Vestibular disease; Zebrafish; α-Tectorin