Auditory transduction in the mouse

Abstract

The sensory hair cells of the mammalian cochlea transduce acoustic stimuli into auditory nerve activity. The biomechanical and molecular details of hair cell mechanotransduction are being acquired at an ever-finer level of resolution. In this review, we discuss how selected mouse mutants and transgenic models have contributed to, and will continue to shape, our understanding of the molecular basis of hair cell mechanotransduction. Functional and structural discoveries made originally in hair cells of nonmammalian vertebrates have been further pursued in the mouse inner ear, where transgenic manipulation can be applied to test molecular mechanisms. Additional insights have been obtained from mice bearing mutations in genes underlying deafness in humans. Taken together, these studies emphasize the elegance of mechanotransduction, enlarge the team of molecular players, and begin to reveal the remarkable adaptations that provide the sensitivity and temporal resolution required for mammalian hearing.

Phenotypic and Expression Analysis of a Novel Spontaneous Myosin VI Null Mutant Mouse

“…Vestibular dysfunction and deafness is, in most cases, caused by abnormalities of stereocilia on inner ear hair cells. Vertebrate inner ear hair cells are mechanosensors that transduce mechanical forces arising from sound waves and head movement providing the sense of hearing and balance, respectively [13,23]. Stereocilia is a mechanically sensitive organelle, which consists of actin filaments, nonmuscle-type myosin and several scaffold proteins [6,10,11].…”

“…Mouse mutations underlying vestibular dysfunction and deafness occur preferentially in genes encoding such proteins. These genes regulate organisation, structure, growth, and function of stereocilia; hence, mutations in these genes often directly affect stereocilia morphology [13,32].…”

Functional auditory hair cells produced in the mammalian cochlea by in utero gene transfer

“… Sensory hair cells in the mammalian cochlea convert mechanical stimuli into electrical impulses that subserve audition1,2. Loss of hair cells and their innervating neurons is the most frequent cause of hearing impairment3.…”

“…The induced hair cells display stereociliary bundles, attract neuronal processes, and express the ribbon synapse marker C-terminal binding protein 2 ( Ctbp2 )12,13. Moreover, the hair cells are capable of mechanoelectrical transduction1,2 and display basolateral conductances with age-appropriate specializations. Our results demonstrate that manipulation of cell fate by transcription factor misexpression produces functional sensory cells in the postnatal mammalian cochlea.…”

Primary processes in sensory cells: current advances

“…Based on groundbreaking electrophysiological studies (Corey and Hudspeth 1979;Hudspeth 1982;Corey and Hudspeth 1983) and the discovery of protein Wlaments connecting the sterocilia within a hair bundle (Pickles et al 1984;Furness and Hackney 1985), a working hypothesis was formulated that explained hair-cell function in terms of a tethered transduction channel (Pickles 1985;Holton and Hudspeth 1986;Hudspeth 1989). An impressive array of excellent biophysical investigations was since carried out to scrutinize and improve this hypothesis (recent reviews: Gillespie et al 2005;Corey 2006;Fettiplace and Hackney 2006;Ricci et al 2006;Grant and Fuchs 2007;Vollrath et al 2007). Today, the tethered-channel hypothesis is well established, and much of the current work is focussed on identifying the molecular components of the transduction complex.…”