A fruit fly's brain may have little edge over its leg bristles when it comes
to telling what time it is. Clocks independently regulated by light abound
throughout a fruit fly's body, report National Institute of Mental Health
(NIMH) -funded researchers in the November 28 issue of Science. By making
them glow like the dials of their mechanical namesakes, the researchers
graphically demonstrated that these tiny timepieces can indeed "take a
lickin' and keep on tickin'."
The scientific team, led by Steve Kay, Ph.D., Scripps Research Institute,
took apart fruit flies to find out if, without any help from their heads,
other body parts would respond to changes in the light/dark cycle.
Strikingly, clock genes, named period, in each separately cultured segment,
turned on and off in unison, according to rhythms set by environmental light
"Under alternating light/dark conditions, the waxing and waning of clock
gene expression was virtually the same in the head, thorax and abdomen,"
said Kay. "Our findings confirm that body clocks run independently in many
tissues outside the brain, implying that cells harbor novel photoreceptors
that aren't involved in vision."
NIMH Director Steven Hyman, M.D., noted that "circadian rhythms, which we
share with all living organisms, influence many human problems, from
adjusting to shift work, to clinical depression, to the timing of cancer
chemotherapy. Using molecular biology to study these rhythms and how they
respond to environmental events, we have recently seen that clock genes are
ubiquitous in mice, and possibly other mammals, including humans. Seeing
the clock genes expressed in fruit flies is a breakthrough."
Kay explained that his team "borrowed a trick from a jellyfish to see where
period was expressed and a trick from a firefly to see when." The
researchers made the clocks glow by engineering transgenic strains of flies
in which the same genes that illuminate a jellyfish and a firefly's tail are
attached to period. The gene for luciferase, the enzyme that glows
intermittently in fireflies, was expressed along with period to reveal when
the clock protein was being produced. Flies were also molecularly altered
to brightly mark the clock sites with Green Fluorescent Protein, which glows
constantly in jellyfish.
The resulting eerie green/yellow photos of the glowing clock gene
expression, produced by co-investigator Jeffrey Plautz of Scripps, are
published on the cover of Science and on the web
Period expression was especially conspicuous in chemosensory cells at the
base of hairs on the legs and wings and on the antennae and beak, prompting
the researchers to speculate that circadian rhythms may regulate a fruit
fly's sensitivity to smell.
Rhythms are known to influence sensitivity to light and pain in mammals. A
variant of period and another similar gene, clock, have recently been found
throughout the bodies of mice. And, there is recent evidence that variants
also exist in humans. Hence, the researchers suggest that even in higher
animals, light itself, rather than the brain, could serve as the "master
oscillator" that coordinates rhythms throughout the organism.
Yet the brain still retains a certain distinction -- even in a fruit fly. In
tissues outside the brain, period gradually dimmed and went out of sync
under conditions of constant darkness, although its normal rhythmicity
recovered after light was reintroduced. Only within the brain did period
stay in sync in the prolonged absence of light. And period in the head has
previously been shown to play a pivotal role in regulating a fruit fly's
Also participating in the research were Maki Kaneko and Jeffrey Hall, Ph.D.,
of the National Science Foundation (NSF) Center for Biological Timing at
Brandeis University. The study was also supported in part by NSF.
NIMH is a component of the National Institutes of Health, an agency of the
U.S. Department of Health and Human Services.
Researcher Steve Kay, Ph.D. (firstname.lastname@example.org), can be reached by
contacting Robin Goldsmith, Scripps Research Institute
(email@example.com), 619-784-8134, or directly at 609-784-2360.