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Development of Outer Hair Cells in Ames Waltzer Mice: Mutation in Protocadherin 15 Affects Development of Cuticular Plate and Associated Structures
Author(s) -
Kikkawa Yayoi S.,
Pawlowski Karen S.,
Wright Charles G.,
Alagramam Kumar N.
Publication year - 2008
Publication title -
the anatomical record: advances in integrative anatomy and evolutionary biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.678
H-Index - 62
eISSN - 1932-8494
pISSN - 1932-8486
DOI - 10.1002/ar.20632
Subject(s) - stereocilia (inner ear) , kinocilium , microbiology and biotechnology , biology , cilium , protocadherin , hair cell , microtubule , morphogenesis , actin , anatomy , inner ear , genetics , cell , cadherin , gene
The Ames waltzer ( av ) mouse mutant harbors a mutation in the protocadherin 15 gene ( Pcdh15 ) and is a model for deafness in Usher syndrome 1F and nonsyndromic deafness DFNB23. Mutation in Pcdh15 affects stereocilia morphogenesis and polarity. Disruptions of apical cellular components in outer hair cells have also been described in av mutants. Organization of stereocilia and cell polarization may be dependent on proper orientation of structural components residing in the apical portion of the cell during development. We used electron and immunofluorescent microscopy to examine structural maturation of outer hair cells in av3J mice with emphasis on the fonticulus, basal body/centriole complex, actin mesh, and the microtubule network during initiation of bundle organization, between embryonic day (E) 16.5 and postnatal day 5 (P5). We found major ultrastructural rearrangements near the hair cell surface in av3J mice. Earliest changes were in kinocilia, basal body, and stereocilia positioning and microtubule arrangement once the kinocilia had lateralized to the side of the cell (between E16.5 and postnatal day [P] 0, before cuticular plate formation and stereocilia elongation). By P0, the developing fonticulus in av mice appeared enlarged, with a normal vesicle density. Stereocilia bundle disorganization increased after P0, with disruptions of the actin mesh within the cuticular plate. These observations support the hypothesis that mutations in Pcdh15 in av3J mice adversely affect coordinated maturation of apical cell components, resulting in disturbed stereocilia bundle polarity in av mice. Anat Rec, 2007. © 2008 Wiley‐Liss, Inc.