title: Distinct roles of Eps8 in the maturation of cochlear and vestibular hair cells.
abstract: Several genetic mutations affecting the development and function of mammalian hair cells have been shown to cause deafness but not vestibular defects, most likely because vestibular deficits are sometimes centrally compensated. The study of hair cell physiology is thus a powerful direct approach to ascertain the functional status of the vestibular end organs. Deletion of Epidermal growth factor receptor pathway substrate 8 (Eps8), a gene involved in actin remodeling, has been shown to cause deafness in mice. While both inner and outer hair cells from Eps8 knockout (KO) mice showed abnormally short stereocilia, inner hair cells (IHCs) also failed to acquire mature-type ion channels. Despite the fact that Eps8 is also expressed in vestibular hair cells, Eps8 KO mice show no vestibular deficits. In the present study we have investigated the properties of vestibular Type I and Type II hair cells in Eps8-KO mice and compared them to those of cochlear IHCs. In the absence of Eps8, vestibular hair cells show normally long kinocilia, significantly shorter stereocilia and a normal pattern of basolateral voltage-dependent ion channels. We have also found that while vestibular hair cells from Eps8 KO mice show normal voltage responses to injected sinusoidal currents, which were used to mimic the mechanoelectrical transducer current, IHCs lose their ability to synchronize their responses to the stimulus. We conclude that the absence of Eps8 produces a weaker phenotype in vestibular hair cells compared to cochlear IHCs, since it affects the hair bundle morphology but not the basolateral membrane currents. This difference is likely to explain the absence of obvious vestibular dysfunction in Eps8 KO mice.
authors.affiliation: Department of Brain and Behavioral Sciences, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Tavazzani
authors.affiliation: Department of Brain and Behavioral Sciences, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Spaiardi
authors.affiliation: Department of Brain and Behavioral Sciences, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy. Electronic address: valeria.zampini@parisdescartes.fr.
authors.forename: Valeria
authors.initials: V
authors.lastname: Zampini
authors.affiliation: Department of Brain and Behavioral Sciences, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy. Electronic address: contini@uic.edu.
authors.forename: Donatella
authors.initials: D
authors.lastname: Contini
authors.affiliation: Department of Brain and Behavioral Sciences, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Manca
authors.affiliation: Department of Brain and Behavioral Sciences, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Russo
authors.affiliation: Department of Brain and Behavioral Sciences, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy.
authors.forename: Ivo
authors.initials: I
authors.lastname: Prigioni
authors.affiliation: Department of Biomedical Science, Sensory Neuroscience Group, Alfred Denny Building (B1 221), University of Sheffield, Western Bank, Sheffield S10 2TN, UK. Electronic address: w.marcotti@sheffield.ac.uk.
authors.forename: Walter
authors.initials: W
authors.lastname: Marcotti
authors.affiliation: Department of Brain and Behavioral Sciences, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy. Electronic address: smasetto@unipv.it.
authors.forename: Sergio
authors.initials: S
authors.lastname: Masetto
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003638:Deafness / Q000378:metabolism / Q000473:pathology; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism* / Q000473:pathology; D018069:Hair Cells, Vestibular / Q000378:metabolism* / Q000473:pathology; D008564:Membrane Potentials / Q000502:physiology; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D010784:Photomicrography; D059547:Stereocilia / Q000378:metabolism / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C083430:Eps8 protein, mouse
keywords: Eps8; K(+) channel; deafness; hair bundle; hair cell; vestibular