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.
Journal
Neuron