title: Spatiotemporal pattern and isoforms of cadherin 23 in wild type and waltzer mice during inner ear hair cell development.
abstract: Mutant alleles of the gene encoding cadherin 23 are associated with Usher syndrome type 1 (USH1D), isolated deafness (DFNB12) in humans, and deafness and circling behavior in waltzer (v) mice. Stereocilia of waltzer mice are disorganized and the kinocilia misplaced, indicating the importance of cadherin 23 for hair bundle development. Cadherin 23 was localized to developing stereocilia and proposed as a component of the tip link. We show that, during development of the inner ear, cadherin 23 is initially detected in centrosomes at E14.5, then along the length of emerging stereocilia, and later becomes concentrated at and subsequently disappears from the tops of stereocilia. In mature vestibular hair bundles, cadherin 23 is present along the kinocilium and in the region of stereocilia-kinocilium bonds, a pattern conserved in mammals, chicks, and frogs. Cadherin 23 is also present in Reissner's membrane (RM) throughout development. In homozygous v(6J) mice, a reported null allele, cadherin 23 was absent from stereocilia, but present in kinocilia, RM, and centrosomes. We reconciled these results by identifying two novel isoforms of Cdh23 unaffected in sequence and expression by the v(6J) allele. Our results suggest that Cdh23 participation in stereocilia links may be restricted to developing hair bundles.
authors.affiliation: Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
authors.forename: Ayala
authors.initials: A
authors.lastname: Lagziel
authors.forename: Zubair M
authors.initials: ZM
authors.lastname: Ahmed
authors.forename: Julie M
authors.initials: JM
authors.lastname: Schultz
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Morell
authors.forename: Inna A
authors.initials: IA
authors.lastname: Belyantseva
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Friedman
mesh_terms: D000483:Alleles; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000096:biosynthesis* / Q000737:chemistry* / Q000378:metabolism; D002448:Cell Adhesion; D018385:Centrosome / Q000378:metabolism; D002642:Chick Embryo; D002923:Cilia / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D007758:Ear, Inner / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D006198:Hair Cells, Auditory / Q000196:embryology*; D006367:HeLa Cells; D006720:Homozygote; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D009154:Mutation; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D013997:Time Factors; D014162:Transfection; D014981:Xenopus
chemical_list: C442480:CDH23 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; C499091:Cdh23 protein, mouse; D018076:DNA, Complementary; D020033:Protein Isoforms