March 23, 2000
Media Contact: Kim McDonald
UCSD STUDY OF UNCOORDINATED FRUIT FLIES PROVIDES
MOLECULAR CLUES TO HEARING PROBLEMS IN
In an ingenious study of severely uncoordinated fruit
scientists at the University of
California, San Diego have obtained the first molecular
of how humans and other complex organisms hear, maintain
balance and sense touch.
In the March 24 issue of Science, the researchers at the
Biology and Howard Hughes Medical Institute report their
of a gene in Drosophila that, when altered, disrupts the
functioning of the fruit flys mechanoreceptor
results in flies that are unable to hear and sense the world
around them, and are so uncoordinated that without help from
the researchers they quickly die.
"You literally have to hand-feed them, put food in
mouths, because theyre so
uncoordinated that they just cant function in any
way," said Richard G. Walker, a
postdoctoral researcher at UCSD and the first author of the
study. Its a lethal mutation, because once they
come out of their pupal cases they are so uncoordinated that
they just fall into their food, which is kind of sticky,
they get stuck and die.
Scientists have known for the past 15 years that mechanical
energy in the form of sound and touch can be transformed by
tiny mechanoreceptor cells into chemical and electrical
that are processed by the brain to hear, sense touch,
balance and determine the position of ones limbs in
Many of these cells, which are found in vertebrate and
animals, consist of tiny hair-like structures that, when
open ion channels in the cells, triggering the release of
which then produce electrical responses in the brain.
The mechanical senses are conserved through
from the tiniest organisms to
humans, because they all perform this critical function,
is to respond to mechanical
stimulation, said Charles S. Zuker, a professor of
who headed the study. Our
enjoyment of wonderful symphonies is nothing but the
of mechanical energy into electrical signals by the cells in
our inner ear.
What scientists have not known is how genes affect the
molecular processes in these mechanoreceptor cells. Such
are typically small and relatively scarce, making it
for researchers to accumulate enough material for
studies. But in Drosophila, the bristles of the
cells on the insects thorax are especially large
making them amenable for biochemical and
studies. Because so many of its genes have been
mapped, the fruit fly is also an ideal organism on which to
conduct genetic studies.
To conduct the study, Walker first screened 27 strains
mutations that made them severely uncoordinated. These
which were isolated six years ago by Maurice Kernan, a
researcher in Zukers lab who is now at the State
of New York at Stony Brook, are thought to have a variety of
mutations that prevent their brains from receiving
their mechanoreceptor cells. However, Walker wanted only
mutants with defects in the mechanoelectrical
transduction pathway itself. He found them by measuring the
electrical currents of their
mechanoreceptor neurons when the hair bristles of the cells
were deflected slightly, an action that in normal insects
a small electrical current. The cells are so sensitive that
a movement that deflects the bristles only a small fraction
of a micrometer can be sensed by the brain.
After Walker found three strains that produced little or no
electrical current, dubbed
nompC for no mechanoreceptor potential C, he
a gene, encoding a novel ion
channel, that when put into nompC flies restored the mutants
to normal. Aarron T. Willingham, a graduate student working
in Zukers lab, tied the defects to mutations in
confirming nompCs identity.
Once they cloned
nompC, everything was
Peter G. Gillespie of the Oregon
Hearing Research Center and Vollum Institute at the
nompC is definitely part of the fly transduction
either the pore itself or a principal component. This
enormous significance as it suggests that one could find
mechanotransduction channels by looking for relatives of nompC.
Identifying any protein that serves within any mechanical
apparatus has been exceptionally difficult. But here we have
a clear answer.
The UCSD researchers found a homologous, or functionally
protein produced by
a similar gene in the roundworm C. elegans. They suspect
similar genes and proteins are found in humans and other
organisms that have retained the same genetic and
machinery as Drosophila and C. elegans through evolution.
theres one thing weve learned over the past
its that model organisms like
Drosophila are wonderful engines of discovery, said
They not only allow us to
efficiently focus on problems that are hard to track in
organisms, they also recapitulate much of the same
more complex forms. In essence, we are nothing but a big
He and his colleagues believe their discovery
could have application in understanding
and treating hearing loss, which is estimated to affect some
30 million Americans.
As hard as it may be to visualize, there are very
developmental and physiological
parallels between mechanosensation as done by fly
by the human inner ear, said James W. Posakony, a
professor at UCSD. So it is quite possible that a
version of this channel protein exists and has a major role
in how we hear. This would be of extreme importance in
both hearing and deafness in humans.
Hearing loss is a major medical problem in
countries, because hearing
loss comes in many different shapes and forms, said
Many are inherited and many are due to abuse.
very likely that both types of human disorders are
tied to defects in the ability of these cells to perform. So
understanding the mechanism of mechanosensory signalling can
produce some very important insights into how to treat,
and diagnose hearing disorders.
# # #
To obtain photos or video, contact Kim McDonald
Photo/Video credit: Richard Walker, UCSD
Photo caption: UCSD scientists have discovered a gene in
uncoordinated strain of Drosophila that, when altered,
the molecular functioning of the fruit fly's mechanoreceptor
cells. Because the physiology of these cells is
to that of cells in the inner ear of humans, their
should provide important insights into how to treat, prevent
anddiagnose human hearing disorders.