The researchers were seeking to understand the role of myosin VIIA, which
had been found to be defective in the inherited human disorder Usher type1B
syndrome, the most common form of combined blindness and deafness in
humans. Mutation of the myosin VIIA gene in Usher syndrome results in an
impaired ability of the auditory nerves to transmit sensory input to the
brain, accompanied by retinitis pigmentosa, a disorder that causes
progressive vision loss.

According to Kiehart, while the origin of the disease had been traced in
humans, and researchers had produced versions of the disorder by
genetically altering mice, much remains unknown about how the defective
myosin protein interferes with hearing.

"This protein is found in both humans and the fruit fly Drosophila, and a
major question was whether it is used in the same way in both species, even
though they have very different hearing mechanisms." Both flies and humans,
however, detect sound through the vibration of receptor cells in their
hearing systems, said Kiehart, and myosin VIIA is involved in both.

The researchers studied mutant versions of the fruit fly called "crinkled,"
provided by Franke and Kiehart. The crinkled mutant lacks a functioning
gene for myosin VIIA in the hearing system. In their experiments, Eberl and
Todi tested whether this defect affected the flies' hearing.

They played the mutant flies a component of the male fly courtship song, as
well as pure tones. They found that the nerve cells connected to the flies'
auditory structures called scolopidia, did not produce neural electrical
signals in response to the sounds, demonstrating that the flies were deaf
due to the nonfunctioning protein.

According to Kiehart, detailed studies of the scolopidia structure of the
mutant flies revealed aberrations in a structure called a "dendritic cap,"
which covers the end of the scolopidia. This cap connects the scolopidia to
the neurons that transmit auditory signals to the brain.

"So, in a way we don't understand, myosin VII actually mediates that
attachment but that's the next frontier in this research," said Kiehart.
"Now, we need to figure out what the myosin is doing to mediate that
attachment."

In their latest studies, the scientists ruled out some possibilities --
that mutant myosin VIIA caused defects in junctions between cells in the
hearing organ or in transporting certain hearing-related proteins. "So, we
have tried some of the more obvious possibilities, and they don't seem to
explain the defect," said Kiehart. "So it's going to be a more subtle
effect." Kiehart said that the new studies showed the value of the fruit
fly as an animal model for studying the defective protein.

"We can use unique genetic strategies in the fruit fly to understand the
machinery of this disorder in a way that can't be done in other animals,"
he said. Such strategies involve using genetic methods to selectively
suppress or enhance the function of many genes, to discover those that
function along with myosin VIIA in hearing. From that understanding, the
researchers can deduce the mechanism by which myosin VIIA works.

Also, said Kiehart, since the fly uses the same myosin VIIA protein for
different purposes throughout its body, study of those other functions
could yield insight into the protein's role in hearing. Such studies will
likely yield insights into the mechanism of hearing loss in humans due to
the defective gene, he said.

"If we can establish how this myosin functions in flies -- what it binds to
and what its role is in establishing the structure -- we will gain insights
into the mammalian system," he said. "While we know that the two types of
hearing structures are different in detail -- like two differently
patterned brick walls -- we do know that they each use the same basic
mortar or the same basic brick."