Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene involved in common birth defect also regulates skin biology

17.10.2006
Following up on an earlier discovery that a gene called IRF6 is involved in the common birth defect cleft lip and palate, researchers at the University of Iowa Roy J. and Lucille A. Carver College of Medicine and their colleagues have identified the function of the gene.

Their latest findings, published online Oct. 15 in Nature Genetics, reveal an unexpected role for IRF6 in the growth and development of skin cells, a discovery that may have implications for wound healing and cancer research.

In 2002, Brian Schutte, Ph.D., UI associate professor of pediatrics and nursing, and Jeff Murray, M.D., UI professor of pediatrics, pediatric dentistry and biological sciences, and the Roy J. Carver Chair in Perinatal Health, led a study showing that mutations in IRF6 cause Van der Woude syndrome (VWS), a rare, dominantly inherited form of cleft lip and palate. Subsequently, the researchers found that this gene also is mutated in 10 to 15 percent of the more common, so-called non-syndromic cases of cleft lip and palate. Cleft lip and palate, where the lip or both the lip and palate (roof of the mouth) fail to close, occurs in approximately one of every 1,000 babies.

In order to determine the function of this gene, the researchers created mice that lacked IRF6. These mice had very abnormal skin as well as a cleft palate. Detailed analysis of the mice revealed that IRF6 regulates the proliferation and differentiation of keratinocytes -- the main cell type in the epidermis or outer layer of skin. Keratinocytes also provide a protective barrier around the mouth, gut, liver, lung, kidney and other internal organs.

... more about:
»CARC »IRF6 »Mutation »Pediatric »abnormal »cleft »cleft lip

"This study really looks at the role of IRF6 in skin development. By focusing on skin we felt we could learn more about this specific cell type that is also abnormal in the palate," Schutte said. "The insight we gained into the function of IRF6 will help focus research efforts to identify other genes involved in cleft lip and palate."

Skin is an extremely important tissue, as it is the largest tissue in the body and it provides a critical external barrier. Normal epidermis has four layers of keratinocytes. The UI study showed that mice that lack IRF6 have abnormal skin development and are missing the upper two cellular layers of the epidermis. The researchers also showed abnormal proliferation of keratinocytes in one of the remaining two layers and failure of these cells to die off or differentiate as normal.

Although humans with Van der Woude syndrome do not have skin defects, a similar human condition, called popliteal ptyergium syndrome (PPS) that is also caused by mutations in IRF6, does cause skin abnormalities in addition to cleft lip and palate. Thus, the UI researchers were not completely surprised by the skin abnormalities in the mice.

Mice provided a particularly good animal model for the UI study because mice and humans have very similar facial development and both share the distinctive mammalian structure of a palate, which separates the nasal airway from the mouth allowing a baby to suckle. In addition, it is fairly easy to create mutations in mice to study a particular gene's function.

"Having an animal model for a major human birth defect like cleft lip and palate provides us with the opportunity to investigate ways to better treat and prevent these disorders much more quickly than was previously possible," Murray said. "Dr. Schutte's work has also expanded our knowledge of other critical areas of human health such as the role of our skin in development and in how wounds and scars may heal."

"Our results open many new avenues of research because the function we discovered for IRF6 is vastly different than the best understood function for the other IRF genes," Schutte added.

IRF6 belongs to a family of nine IRF genes, which have been extensively investigated. The UI study reveals that IRF6 has a different function than the other known IRF genes, which are all primarily involved in the immune response. Its newly identified role in cell proliferation and differentiation may mean that IRF6 also is involved in other medically important areas of biology such as cancer and wound healing.

The main funding for the study is from a National Institute of Dental and Craniofacial Research grant for the UI Craniofacial Anomalies Research Center (CARC). Murray is the principal investigator for the grant. The CARC also supported a complementary study by researchers at the University of Manchester in England, who are collaborating with Schutte and Murray. The Manchester team investigated a different mutation in the mouse IRF6 gene and observed similar results to the UI study. This second study will also be published in Nature Genetics.

"The support from the CARC was critical to the completion of these two studies because several different disciplines were needed to characterize the abnormalities of the mice," Schutte said. "The CARC brought together specialists to attack the problem from many different directions."

Dave Pedersen | EurekAlert!
Further information:
http://www.uiowa.edu

Further reports about: CARC IRF6 Mutation Pediatric abnormal cleft cleft lip

More articles from Life Sciences:

nachricht Transforming plant cells from generalists to specialists
07.12.2016 | Duke University

nachricht What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Predicting unpredictability: Information theory offers new way to read ice cores

07.12.2016 | Earth Sciences

Sea ice hit record lows in November

07.12.2016 | Earth Sciences

New material could lead to erasable and rewriteable optical chips

07.12.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>