Biological Clocks No Longer Found Only In 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.