title: The deaf mouse mutant whirler suggests a role for whirlin in actin filament dynamics and stereocilia development.
abstract: Stereocilia, finger-like projections forming the hair bundle on the apical surface of sensory hair cells in the cochlea, are responsible for mechanosensation and ultimately the perception of sound. The actin cytoskeleton of the stereocilia contains hundreds of tightly cross-linked parallel actin filaments in a paracrystalline array and it is vital for their function. Although several genes have been identified and associated with stereocilia development, the molecular mechanisms responsible for stereocilia growth, maintenance and organisation of the hair bundle have not been fully resolved. Here we provide further characterisation of the stereocilia of the whirler mouse mutant. We found that a lack of whirlin protein in whirler mutants results in short stereocilia with larger diameters without a corresponding increase in the number of actin filaments in inner hair cells. However, a decrease in the actin filament packing density was evident in the whirler mutant. The electron-density at the tip of each stereocilium was markedly patchy and irregular in the whirler mutants compared with a uniform band in controls. The outer hair cell stereocilia of the whirler homozygote also showed an increase in diameter and variable heights within bundles. The number of outer hair cell stereocilia was significantly reduced and the centre-to-centre spacing between the stereocilia was greater than in the wildtype. Our findings suggest that whirlin plays an important role in actin filament packing and dynamics during postnatal stereocilium elongation.
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich, United Kingdom. m.mogensen@uea.ac.uk
authors.forename: Mette M
authors.initials: MM
authors.lastname: Mogensen
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Rzadzinska
authors.forename: Karen P
authors.initials: KP
authors.lastname: Steel
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D003051:Cochlea / Q000378:metabolism / Q000648:ultrastructure; D003638:Deafness / Q000235:genetics / Q000378:metabolism*; D007758:Ear, Inner / Q000378:metabolism / Q000648:ultrastructure; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism / Q000648:ultrastructure*; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism / Q000648:ultrastructure; D006720:Homozygote; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D008855:Microscopy, Electron, Scanning; D009154:Mutation; D011506:Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins; C440007:Strc protein, mouse; C477218:Whrn protein, mouse