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NSF PR 97-70 - November 27, 1997
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Biological Clocks No Longer Found Only in the Brain
A recent discovery by a team of scientists, working
in part through the National Science Foundation (NSF)'s
Center for Biological Timing, challenges the strongly-held
belief that 24-hour rhythms (biological clocks) are
centrally controlled by the brain.
Using the fruit fly as a model system to study circadian
rhythms, the researchers -- led by cell biologist
Steve Kay of the Scripps Research Institute in San
Diego, California -- sought to determine whether individual
body parts would respond to changes in the light/dark
cycle. In each appendage, clock genes turned on and
off in unison, according to rhythms set by environmental
light manipulations.
The scientists hope that understanding the location
of the clock tissues and cells, as well as identifying
which genes and proteins make up the biological cogs,
will lead to new strategies for the treatment of disorders
associated with jet lag, shift work and seasonal depression.
"These results are fundamental to understanding how
the timing of cellular functions is integrated in
complex organisms," says Christopher Platt, program
director in NSF's neuroscience program. "This advance
shows how basic research with a model system has a
broad impact on fields from agriculture to human biology."
According to Kay, "Our findings confirm that body
clocks run independently in many tissues outside the
brain, and are reset by light, implying that cells
harbor novel photoreceptors that aren't involved in
vision."
The researchers borrowed some tricks from the world
of bioluminescent organisms, to measure the genes
that control clocks in animals. They fused the fruit
flies' clock DNA to "glow" genes either from jellyfish
or fireflies, to make glow-in-the-dark fruit flies.
Kay commented, "We found that all tissues we cultured
from the whole animal were glowing on and off, demonstrating
that lots of clocks are running throughout the fly,
independently of the brain." Under normal light/dark
conditions, the clock genes rhythmically luminesced
in each of the segments -- head, thorax and abdomen.
The clock genes were especially conspicuous in chemosensory
cells at the base of hairs on the legs and wings and
on the antennae and proboscis.
These clocks also ebbed and flowed autonomously in
response to light, suggesting that circadian rhythms
likely regulate a fruit fly's sense of smell, much
as they influence light and pain sensitivity in mammals.
While the authors raise the possibility that this
evidence challenges the current notions about the
role of the brain as the seat that coordinates rhythms
throughout the organism, they acknowledge that the
brain still retains a certain distinction, even in
a fruit fly. In the prolonged absence of light, the
brain was the only organ in which the clock genes
remained in sync.
A mammalian variant of the clock gene recently was
identified, and another similar gene also has been
found throughout the body of mice. According to Kay,
the discovery of many non-brain clocks in fruit flies
could well be true for humans. "In this case it might
mean that our skin, liver or other peripheral tissues
have their own clocks to control these local functions,"
he suggests.
Participating in the research were scientists Jeffrey
Plautz of the Scripps Research Institute and Maki
Kaneko and Jeffrey C. Hall of Brandeis University.
The study was also funded in part by the National
Institute of Mental Health of the National Institutes
of Health.
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