Although researchers know a great deal about the biophysical basis of hearing, not much is known about the molecules which are required for mechanotransduction in vertebrate sensory hair cells. In Christiane Nüsslein-Volhard's laboratory at the Max Planck Institute of Developmental Biology in Tübingen/Germany, a new study on zebrafish mutants with problems in balance has lead to the identification of eight genes which are required for inner ear and lateral line function. Five of these genes appear to have a specific role within sensory hair cells since they are required for the production of extracellular potential generation, a measure of hair cell function.
The results of the study can be found in the February issue of Neuron (Nicolson et al . 1998). A strong point of the work is the analysis of the zebrafish mutants at different levels of neurobiology, from behavior and anatomy to physiology. This was achieved by fruitful collaboration between scientists at the Max Planck Institute of Developmental Biology and the Ear, Nose, and Throat Clinic in Tübingen, Germany.
The zebrafish vestibular/auditory mutants are similar to mice shaker/waltzer type mutants in that they also make circular motions and have problems with maintaining balance. Behavioral tests suggest that some of these zebrafish mutants do not sense gravity, i.e. they swim as if they are in a weightless environment. A major advantage of using zebrafish to study the inner ear is the transparency of the larval organ which allows researchers to directly view sensory hair cells in live fish. In addition, the transparent larvae are suitable for imaging of neuronal activity within the brain and peripheral nervous system.
Localization of the defects to the sensory hair cells or primary neurons in the mutants was achieved by a non-invasive technique of labeling early embryos with a fluorescent calcium indicator and subsequent imaging of calcium transients in hindbrain neurons in response to vibrational stimuli. Further physiological studies of mechanosensation in the sensory hair cells in the larval lateral line (which are very similar to inner ear sensory cells) narrowed the defects down to the level of mechanotransduction in five of the mutants. Future work will be devoted to cloning the genes with the hope of gaining insight into the molecular basis of mechanotransduction in vertebrates.
Neuron