Molecular Genetics of the Mechanical Senses


Maurice Kernan
Maurice Kernan
Assistant Professor
PhD, University of Wisconsin

Emiko Higashijima - Research Scientist
James Baker - postdoctoral fellow
Yun Doo Chung - postdoctoral fellow
We use genetics, molecular biology and electrophysiology to study sensory cell function, with Drosophila as our model system. Our aim is to discover the molecular basis of the mechanical senses. These include not only hearing and touch, but also balance and proprioception - senses we rely on utterly, but take for granted unless they become defective. In all these senses, the initial event is the conversion of a mechanical stimulus into a change in the membrane potential of a sensory cell. But little is known about the molecular mechanism by which this is accomplished - far less than is known about the mechanism of any other sensory mode.

Mechanosensory cells are biochemically intractable: they are usually scattered and embedded in other cell types. The receptors and channels involved are likely few in number, and may be quite unlike the molecules that mediate other modes of signal transduction. To surmount these obstacles, we are using a genetic strategy which enables functional elements to be identified, no matter how rare and mysterious they be. The wealth of genetic materials and techniques provided by Drosophila, together with the ability to record the electrophysiological response from its mechanosensory neurons, makes it an ideal system for the job. Physiological and developmental similarities between Drosophila bristles and vertebrate hair cells - the sensory elements in our inner ear - hint at a common underlying transduction mechanism.

We identify genes of interest by isolating mutations that affect mechanosensory behavior, resulting in flies that are touch-insensitive and severely uncoordinated. Extracellular recording from single bristles shows that mutant sensory neurons fail to generate a receptor potential in response to mechanical stimulation. Recently, we have developed a technique for recording from the fly’s auditory system, and have found that almost all of our touch-insensitive mutants are also deaf, suggesting that a shared molecular mechanism underlies the senses of touch and hearing in Drosophila. In addition, mutations in the beethoven and tilB genes cause axonemal defects and specifically affect hearin, suggesting a role for ciliary dynamics in auditory signal transduction.

We are now isolating the affected genes using classical and novel positional cloning techniques, so as to characterize the gene products and define their particular functions. Longer term projects include intracellular recording from mechanosensory neurons in culture or in situ, and ultrastructural analyses of the mutant mechanosensory organs. Our eventual aim is to model at the molecular level the working parts of a cellular mechanotransducer.

M. Kernan, D. Cowan, and C. Zuker (1994). Genetic dissection of mechanotransduction: Drosophila mutations
defective in mechanoreception. Neuron 12, 1195-1206.

M. Kernan & C. Zuker (1995). Genetic approaches to mechanosensory transduction Current Opinion in
Neurobiology 5 443-448.

M. Kernan (1997). The molecular basis of the mechanical senses: One mechanism or many? (commentary).
The Journal of NIH Research 10 32-36.

D. F. Eberl, R.W. Hardy and M. Kernan (1999). A single transduction mechanism mediates touch and hearing
in Drosophila. (in preparation).

WANTED: volunteers for experiments to discover the molecular bases of touch, hearing and proprioception. Room and board provided. Desired qualities: congenital insensitivity to one's colleagues and surroundings; little attention to cleanliness; a tendency to breed indiscriminately, and six or more legs. A total lack of motor coordination is a plus.