The Rockefeller University - Laboratory of Sensory Neuroscience

Hair Cells of the Inner Ear

Screening for Zebrafish Mutations Affecting
Hearing and Balance

Mutation of the Zebrafish's choroideremia Gene
Causes Hair-Cell Degeneration

Paravalbumin 3, A Potent Ca²⁺ Buffer in Hair Cells

Spontaneous Oscillation by Hair Bundles

Electrical Stimulation of Hair-Bundle Movement

Electron-Microscopic Tomographic Analysis of
the Transduction Element

Radixin in the hair bundle

Dynamical instability and the ear's active process

Sunday, July 20, 2008




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Screening for Zebrafish Mutations Affecting Hearing and Balance

The mechanosensory receptor of the auditory system, the hair cell, is poorly understood at a molecular level. Genetic analysis provides an unbiased means of identifying novel proteins of functional importance in hearing. Hair cells are unique to vertebrates, however, so they almost certainly contain constituents that cannot be identified by genetic screens of invertebrates. We have therefore used morphological and behavioral screens to identify mutations affecting acousticolateralis organs in the most genetically tractable vertebrate organism, the zebrafish (Danio rerio). The lateral-line organ provides one convenient system in which to assay the effects of mutations. Hair cells on a zebrafish's surface can be selectively labeled by immersion of the animal in a fluorescent dye that accumulates in normal hair cells after entry through their mechanoelectrical- transduction channels. Because abnormalities in hair-cell development or function are manifested by diminished or absent labeling, mutant lines may then be isolated by examining young fish under a fluorescence dissecting microscope. A second screening methodology identifies fish with mutations that affect hair cells in the internal ear. Zebrafish have relatively acute hearing: abrupt acoustic stimulation of zebrafish triggers a startle reflex that helps the animals evade predators. Excitation of saccular hair cells initiates this highly stereotyped response, in which an animal moves from its relaxed, extended posture to a C-shaped configuration in about one-hundredth of a second. We have identified several mutant lines in which fish fail to execute a normal startle reflex. Having isolated 17 mutant lines defective in the development or function of the inner ear or lateral-line organ, we are now engaged in the positional cloning and characterization of the affected genes.