Buenos 'notch-es': Universal signaling pathway found to regulate sleep

May 5, 2011

Sleeping worms have much to teach people, a notion famously applied by the children's show "Sesame Street," in which Oscar the Grouch often reads bedtime stories to his pet worm Slimy. Based on research with their own worms, a team of neurobiologists at Brown University and several other institutions has now found that "Notch," a fundamental signaling pathway found in all animals, is directly involved in sleep in the nematode C. elegans.

"This is a major player in development across all animal species," said Anne Hart, associate professor of at Brown. "The fact that this highly conserved pathway regulates how much these little animals strongly suggests that it's going to play a critical role in other animals, including humans. The in this pathway are expressed in the human ."

The work, to be published May 24 in the journal , offers new insights into what controls sleep. The lead authors are Komudi Singh, a postdoctoral fellow in the Department of Neuroscience at Brown University, and Michael Chao, a previous member of the Hart laboratory, who is now an associate professor at California State University–San Bernardino.

"We understand sleep as little as we understand consciousness," said Hart, the paper's senior author. "We're not clear why sleep is required, how animals enter into a sleep state, how sleep is maintained, or how animals wake up. We're still trying to figure out what is critical at the cellular level and the molecular level."

Ultimately, Hart added, researchers could use that knowledge to develop more precise and safer sleep aids.

"We only have some really blunt tools that we can use to change sleep patterns," she said. "But there are definite side effects to manipulating sleep the way we do now."

Mysterious napping

Hart first realized that Notch pathway genes might be important for sleep when her group was investigating an entirely different behavior. She was studying the effect of this pathway on the nematodes' revulsion to an odious-smelling substance called octanol. What she found, and also reports in the Current Biology paper, is that adult nematodes without Notch pathway genes (like osm-11) have their Notch receptors turned off and, therefore, they do not avoid octanol as normal worms do.

But she was shocked to find that the adult nematodes in which the osm-11 gene was overexpressed were doing something quite bizarre. "Normally, adult nematodes spend all of their time moving" she said. "But, these animals suddenly start taking spontaneous 'naps.' It was the oddest thing I'd seen in my career."

sleep is not exactly the same as sleep in larger animals, but these worms do go into a quiescent sleep-like state when molting. The worms with too much osm-11 were dozing when they were not supposed to.

Other experiments showed that worms lacking osm-11 and the related osm-7 genes were hyperactive, exhibiting twice as many body bends each minute as normal nematodes.

The story became clear. The more Notch signaling was turned on, the sleepier the worms would be. When it is suppressed, they go into overdrive and become too active.

In humans, the gene that is most similar to osm-11 is called Deltalike1 (abbreviated DLK1). It is expressed in regions of the brain associated with the sleep-wake cycle.

Beyond Notch

That result alone is not enough to lead directly to the development of a new sleep drug, even for . Notch signaling is implicated in a lot of different activities in the body, Hart said, some of which should not be encouraged.

"Too much Notch signaling can cause cancer, so we would have to be very targeted in how we manipulate it," she said. "One of the next steps we're going to take is to look at the specific steps in Notch signaling that are pertinent to arousal and quiescence."

Focusing on those steps could minimize side effects, Hart said.

Related Stories

Recommended for you

Study finds harmful protein on acid triggers a life-threatening disease

July 27, 2017
Using an array of modern biochemical and structural biology techniques, researchers from Boston University School of Medicine (BUSM) have begun to unravel the mystery of how acidity influences a small protein called serum ...

CRISPR sheds light on rare pediatric bone marrow failure syndrome

July 27, 2017
Using the gene editing technology CRISPR, scientists have shed light on a rare, sometimes fatal syndrome that causes children to gradually lose the ability to manufacture vital blood cells.

Brain cells found to control aging

July 26, 2017
Scientists at Albert Einstein College of Medicine have found that stem cells in the brain's hypothalamus govern how fast aging occurs in the body. The finding, made in mice, could lead to new strategies for warding off age-related ...

Post-stroke patients reach terra firma with new exosuit technology

July 26, 2017
Upright walking on two legs is a defining trait in humans, enabling them to move very efficiently throughout their environment. This can all change in the blink of an eye when a stroke occurs. In about 80% of patients post-stroke, ...

Molecular hitchhiker on human protein signals tumors to self-destruct

July 24, 2017
Powerful molecules can hitch rides on a plentiful human protein and signal tumors to self-destruct, a team of Vanderbilt University engineers found.

Researchers develop new method to generate human antibodies

July 24, 2017
An international team of scientists has developed a method to rapidly produce specific human antibodies in the laboratory. The technique, which will be described in a paper to be published July 24 in The Journal of Experimental ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.