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 A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>