Cleft palate is one of the most common congenital birth defects, occurring in one out of every 700 live births. Clefts are more common in children of American Indian, Hispanic or Asian descent. While males are twice as likely to have a cleft lip, females are twice as likely to have a cleft palate.
But genes are not the only factor influencing the malformation says, Yang Chai, professor and director of the USC School of Dentistry's Center for Craniofacial Molecular Biology.
Researchers around the world believe that most cases of cleft lip and cleft palate are caused by an interaction of genetic and environmental factors; however, a specific cause may not be discovered for every baby.
Growth factors responsible for development, including palate and tooth formation, have more than one way to direct cells to make changes, says Chai.
The Discovery by the USC team is spotlighted in the August 12 issue of Development Cell.
Chai's group, which includes fellow CCMB researchers Xun Xu, Jun Han, Yoshihiro Ito and Pablo Bringas Jr., has been specifically scrutinizing the transforming growth factor beta (TGF-ß) family's role in palate formation problems.
The TGF- ßs are not only involved in palate formation, they plays an important development role all over the body. They work by binding to cell surface receptors and activating signaling molecules within the cell. These signaling molecules then travel to the nucleus, the cell's control center, and prompt DNA expression in order to spur changes in the cell.
"For instance, we've learned that when someone has a haploid insufficiency and is missing one copy of the TGF-ß gene, he or she is more vulnerable to environmental insults that can cause cleft palate, such as drugs, smoking and alcohol," Chai says.
Smad4 is one of the main signaling molecules used in the TGF-ß pathway during palate and tooth development. Chai says his team had initially hypothesized that since irregularities in the TGF-ß gene or its cell surface receptors sparked palate malformation in experimental mouse models, knocking out the Smad4 genes would do the same.
"We found that if we blocked TGF-ß or the receptors, a cleft palate develops," he says, "But when Smad4 was blocked, normal palate epithelium still covered the palatal shelf.
The team found that p38 MAPK (mitogen activated protein kinase) can take Smad4's place in the pathway and signal DNA expression to form the palate. Normally serving as a stress-response protein and activated by environmental insults, such as ultraviolet radiation on skin cells, p38 MAPK appears to act as a "spare tire" when Smad4 function is compromised, Chai says. When either one or the other is inactivated, the palate epithelium will still form properly, failing to form only if both signaling molecules are knocked out.
P38 MAPK isn't a perfect replacement for Smad4 during oral development –when Smad4 is nonfunctional, teeth only partially form – but the results are still surprising for a molecule better known for its roles during cancer, Chai says.
Further study could have big implications not only on congenital oral birth defects like cleft palate but also on malformations and diseases in tissues throughout the body, and patients could one day be able to take advantage of new genetic counseling and treatment methods stemming from this information, he hopes.
For new parents this latest development offers hope for the future. Those individuals with a family risk of either cleft lip or cleft palate can seek counseling early on and identify craniofacial teams that will assist them in following the best treatment plans for their child.
In addition, the discovery opens up other opportunities for researchers and clinicians.
"This information is useful not just for palate and teeth but also for cancer and cell biology in general," he says. "Ultimately, we have to be translational in order to make ourselves useful to patients."
Angelica Urquijo | EurekAlert!
Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology
Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster
High-precision measurement of the g-factor eleven times more precise than before / Results indicate a strong similarity between protons and antiprotons
The magnetic moment of an individual proton is inconceivably small, but can still be quantified. The basis for undertaking this measurement was laid over ten...
Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
24.11.2017 | Earth Sciences
24.11.2017 | Ecology, The Environment and Conservation
24.11.2017 | Earth Sciences