Nav: Home

Study finds link between fragile X syndrome gene and dysregulated tissue growth

December 05, 2017

BLOOMINGTON, Ind. -- Researchers at Indiana University have found a previously undetected link between the gene that causes fragile X syndrome and increased tissue growth. The link could reveal a key biological mechanism behind the serious physical and mental impairments caused by the disorder.

An inheritable genetic condition, fragile X syndrome is estimated to cause mild to moderate intellectual disabilities in 1 in 4,000 to 5,000 males and 1 in 6,000 to 8,000 females. It also causes physical abnormalities such as large brain size and weight at birth, unusually fast growth in height, gastrointestinal issues and high risk of obesity.

The study, which was conducted in fruit flies, focused on the effects of losing the same protein that's missing in people with fragile X syndrome on the intestines of insects modified to model the disease. The work is reported in the journal Cell Reports.

"To our knowledge, this is the first study to find a stem-cell-based mechanism by which a protein that is absent in people with fragile X syndrome limits excessive organ growth," said Arthur Luhur, a research associate in the IU Bloomington College of Arts and Sciences' Department of Biology, who is the lead author on the study. "This could represent a root cause for the gastrointestinal problems seen in people with the condition."

Similarly, Luhur said the stem-cell-based mechanism could cause symptoms seen in other parts of the body in fragile X syndrome, such as accelerated height growth from unrestrained activity in the bones' stem cells, or mental problems caused by excess neurons.

He also noted that basic biological research into fragile X syndrome's non-neurological symptoms is important since these effects are understudied -- and therefore undertreated -- compared to problems with mental development.

Fragile X syndrome is caused by an error in a single gene in the X chromosome called FMR1. Typically, the FMR1 gene creates a protein called FMRP. In individuals with fragile X syndrome, an abnormality in this gene causes the body to "silence" the production of FMRP.

The IU team found that the absence of FMRP causes a higher rate of cellular growth -- driven by symmetric stem cell division. Typically, this process is balanced by asymmetric stem cell division, when old cells are replaced with new ones.

"The cells that lacked FMRP acted like cars without brakes," said Nicholas Sokol, an associate professor in the Department of Biology, who is the senior author on the study. "They were ready to divide more often and more quickly, and they tended to divide symmetrically, causing the intestine to be bigger than normal."

The discovery grew from the researchers' earlier research into another gene, called LIN-28, that also appeared to affect growth in the intestinal cells in fruit flies. During that study, IU researchers came across evidence that FMRP -- the protein encoded by the gene that causes fragile X syndrome -- played a role in the same biomolecular pathway as LIN-28.

The earlier study found that lower levels of LIN-28 reduced insulin receptors in the intestines. The reduced number of insulin receptors slowed cellular growth. The new study found that stem cells from the intestines of flies whose genes contained the genetic mutation for fragile X syndrome activated these insulin receptors at a higher rate than normal cells. Moreover, the IU scientists found that higher levels of FMRP affected LIN-28 levels, but not vice versa, suggesting that FMRP plays a controlling role in the biological pathway.

The research may also open doors to research on new treatments of fragile X syndrome, Luhur said. For example, the study found that normal cell growth could be restored by reducing the insulin-signaling activity in fruit flies' intestines using genetic interventions or changes in nutrition. The connection between insulin receptor activity and intestinal growth may also provide new insight into other research, which has shown that the FDA-approved diabetes drug Metformin seems to alleviate some of the neurological symptoms of fragile X syndrome.

"The next step is conducting additional research on FMR1 and LIN-28 in animals to learn more about their biochemical relationship and their effect on metabolism in the body," Luhur said. "These are important questions for understanding how their interaction affects physiology and human health."
-end-
Additional researchers on the study were IU graduate students Kasun Buddika, Ishara Surangi Ariyapala and Shengyao Chen. This work was supported in part by the National Institutes of Health.

Indiana University

Related Stem Cells Articles:

A protein that stem cells require could be a target in killing breast cancer cells
Researchers have identified a protein that must be present in order for mammary stem cells to perform their normal functions.
Approaching a decades-old goal: Making blood stem cells from patients' own cells
Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body.
New research finds novel method for generating airway cells from stem cells
Researchers have developed a new approach for growing and studying cells they hope one day will lead to curing lung diseases such as cystic fibrosis through 'personalized medicine.'
Mature heart muscle cells created in the laboratory from stem cells
Generating mature and viable heart muscle cells from human or other animal stem cells has proven difficult for biologists.
Mutations in bone cells can drive leukemia in neighboring stem cells
DNA mutations in bone cells that support blood development can drive leukemia formation in nearby blood stem cells.
Scientists take aging cardiac stem cells out of semiretirement to improve stem cell therapy
With age, the chromosomes of our cardiac stem cells compress as they move into a state of safe, semiretirement.
Purest yet liver-like cells generated from induced pluripotent stem cells
A team of researchers from the Medical University of South Carolina and elsewhere has found a better way to purify liver cells made from induced pluripotent stem cells.
Stem cell scientists discover genetic switch to increase supply of stem cells from cord blood
International stem cell scientists, co-led in Canada by Dr. John Dick and in the Netherlands by Dr.
Stem cells from diabetic patients coaxed to become insulin-secreting cells
Signaling a potential new approach to treating diabetes, researchers at Washington University School of Medicine in St.

Related Stem Cells Reading:

Stem Cell Therapy: A Rising Tide: How Stem Cells Are Disrupting Medicine and Transforming Lives
by Neil H Riordan (Author)

Stem Cells: A Short Course
by Rob Burgess (Author)

Essentials of Stem Cell Biology
by Robert Lanza (Editor), Anthony Atala (Editor)

The Science of Stem Cells
by Jonathan M. W. Slack (Author)

Stem Cells: Promise And Reality
by Lygia V Pereira (Author)

The Stem Cell Revolution
by Mark Berman MD (Author), Elliot Lander MD (Contributor)

Stem Cells For Dummies
by Lawrence S.B. Goldstein (Author), Meg Schneider (Author)

Stem Cells: An Insider's Guide
by Paul Knoepfler (Author)

Stem Cell Revolution: Discover 26 Disruptive Technological Advances to Stem Cell Activation
by Joseph Christiano (Author)

Engineering Stem Cells for Tissue Regeneration
by Ngan F Huang (Author), Ngan F Huang (Editor), Nicolas L'Heureux (Editor), Song L (Editor)

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Hacking The Law
We have a vision of justice as blind, impartial, and fair — but in reality, the law often fails those who need it most. This hour, TED speakers explore radical ways to change the legal system. Guests include lawyer and social justice advocate Robin Steinberg, animal rights lawyer Steven Wise, political activist Brett Hennig, and lawyer and social entrepreneur Vivek Maru.
Now Playing: Science for the People

#495 Earth Science in Space
Some worlds are made of sand. Some are made of water. Some are even made of salt. In science fiction and fantasy, planet can be made of whatever you want. But what does that mean for how the planets themselves work? When in doubt, throw an asteroid at it. This is a live show recorded at the 2018 Dragon Con in Atlanta Georgia. Featuring Travor Valle, Mika McKinnon, David Moscato, Scott Harris, and moderated by our own Bethany Brookshire. Note: The sound isn't as good as we'd hoped but we love the guests and the conversation and we wanted to...