Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mutant flies shed light on inherited intellectual disability

05.07.2011
Clumsy fruit flies with poor posture are helping an international team of scientists understand inherited intellectual disability in humans – and vice versa.

The flies can't hold their wings tightly against their bodies, and have trouble with flying and climbing behaviors, because they have mutations in a gene called dNab2. In humans, mutations in the same gene (with a clunkier name, ZC3H14) have been found to cause intellectual disability (ID) in studies of some Iranian families. ID describes the condition that was previously called mental retardation.

The protein encoded by Nab2/ZC3H14 appears to be part of a group of proteins, including the one disrupted in fragile X syndrome, that regulate brain cell function by binding RNA.

Cross-species comparisons of Nab2/ZC3H14's function are shedding light on how brain cells regulate genes by controlling the length of their RNA "tails." The results are published online in this week's Proceedings of the National Academy of Sciences Early Edition.

This unusual collaboration brought together investigators from Emory University School of Medicine in Atlanta, the Max Planck Institute for Molecular Genetics in Berlin and the University of Social Welfare and Rehabilitation Sciences in Tehran.

The paper's co-first authors are Emory graduate student Chang Hui Pak and Max Planck postdoc Masoud Garshasbi, with senior authors Andreas Kuss, PhD, group leader at the Max Planck Institute, and Anita Corbett, PhD, professor of biochemistry and Ken Moberg, PhD, assistant professor of cell biology at Emory University School of Medicine.

At Emory, Corbett had studied Nab2 in yeast since the 1990s. Her laboratory teamed up with Moberg to look at the function of the gene in fruit flies. Pak, a student in both Corbett's and Moberg's labs, generated flies with mutations in dNab2.

What made those flies easy to spot, next to regular flies, was that the mutant flies kept their wings stretched out. Healthy flies hold their wings folded together over their bodies. Several mutations that affect nerve or muscle development display this "wings held out" effect in flies, Moberg says.

"At this point, we didn't know if it was a problem with the muscles connected to the wings, or with the nerve networks that control those muscles," he says.

Unexpectedly, Corbett received an e-mail in 2009 providing a flash of insight. The Berlin/Tehran team had been studying families in Iran in which cousins marry, looking for genetic mutations that lead to intellectual disability.

"It has been more straightforward to find mutations that cause ID along the X chromosome, because they show up easily in boys – and they don't need to have inherit the defective genes from both parents," Moberg says. "Studying these families with blood-related parents is a way to explore new ground and learn more about genes on other chromosomes that can be linked to ID."

The Berlin/Tehran team had found that a mutation in the ZC3H14 gene showed up in two independent family trees affected by intellectual disability. Affected individuals can be male or female and have "non-syndromic" intellectual disability, meaning that they don't have altered anatomical development or other features such as autism.

The mutations in ZC3H14 in affected individuals don't completely wipe out production of the protein. This may be why the consequences of the human mutation aren't completely fatal. Puzzlingly, one form of the protein enriched in the brain is still there, but the forms of the protein found all over the body are gone.

"We suspect that the only reason these people are walking around is because that one isoform is still there," Moberg says.

The discovery of the fly/human link has led to a bundle of new questions. The protein Nab2/ZC3H14 binds "poly-A tails" (flags the cell puts on RNA molecules when they're ready to be decoded into protein). The protein restricts the length of the tails, which may be more important for some genes than others, Moberg says.

At Emory, scientists are studying the mutant flies to figure out more precisely what's wrong with them: which cells in the fly's brain are affected and what genes and processes go awry in these cells. Although the overall structure of the brain and nervous system in mutant flies looks OK, preliminary evidence suggests the mutation alters structures in the brain important for learning and memory. Collaborator Gary Bassell is collaborating with Corbett to engineer mice lacking the ZC3H14 gene.

"Although mice may better reflect the human situation, exploring the function of Nab2 in flies first allowed us to be quicker and nimbler in designing experiments," Moberg says.

The Berlin/Tehran team is now examining how common mutations in ZC3H14 are in population groups outside Iran, and whether it can account for other forms of intellectual disability.

The research was supported by the National Institutes of Health, the German Federal Ministry of Education and Research, the Max Planck Innovation Fund and the Iranian National Science Foundation.

Reference: CH Pak et al Mutation of the conserved polyadenosine RNA binding protein ZC3H14/dNab2, impairs neural function in Drosophila and humans. PNAS Early Edition (2011).

Writer: Quinn Eastman

Holly Korschun | EurekAlert!
Further information:
http://www.emory.edu

More articles from Life Sciences:

nachricht Rochester scientists discover gene controlling genetic recombination rates
23.04.2018 | University of Rochester

nachricht One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Tiny microenvironments in the ocean hold clues to global nitrogen cycle

23.04.2018 | Earth Sciences

Joining metals without welding

23.04.2018 | Trade Fair News

Researchers illuminate the path to a new era of microelectronics

23.04.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>