Navigation Links
Growth factor gene shown to be a key to cleft palate
Date:2/2/2010

Cleft palate has been linked to dozens of genes. During their investigation of one of these genes, researchers at Washington University School of Medicine in St. Louis were surprised to find that cleft palate occurs both when the gene is more active and when it is less active than normal.

They say the finding suggests this gene and processes closely associated with it are central to palate development and could become important targets for investigators seeking nonsurgical treatments to prevent cleft palate before birth. Their report will appear in an upcoming issue of the Proceedings of the National Academy of Sciences.

"Palate formation in the embryo is a complex process, and many things can go wrong," says senior author David M. Ornitz, M.D., Ph.D., Alumni Endowed Professor of Developmental Biology. "A cleft palate is often diagnosed late in pregnancy and treated surgically after birth. But if we understood the genetic causes of this common birth defect, we might be able to diagnose it much earlier. That would potentially allow intervention with prenatal surgery or with drugs or other agents designed to counteract the genetic abnormalities."

Clefts of the lip and palate affect about one in 700 newborns worldwide. Children with cleft lip and palate can have difficulty feeding as infants and can have speech, dental and hearing problems as they grow older. Depending on severity, surgical repair can require several operations over many years, and the estimated average lifetime cost of treatment in the United States is about $100,000 per patient.

"We believe the more information we have on the causes of cleft palate, the better hope we have for possibly preventing and more effectively treating the condition," says lead author Alison K. Snyder-Warwick, M.D., a plastic surgery resident at Barnes-Jewish Hospital.

Although some cases of cleft lip and palate are linked to environmental factors such as maternal smoking, viral infections or certain medications, genetic variations play a significant role in many cases. The Washington University researchers studied the fibroblast growth factor receptor 2 (FGFR2) gene, which earlier research has implicated in cleft palate.

They focused on mice with Crouzon syndrome, a developmental disorder caused by a mutation in FGFR2. The mutation activates the receptor and results in a syndrome that is characterized by abnormal development of the skull, face and mouth and is associated with an increased incidence of cleft palate.

In effect, the FGFR2 mutation prevents specific growth signals from being switched off. Normally, the signals would be turned on and off in a carefully orchestrated manner to ensure proper patterns of growth and development of embryonic tissues. However, the Crouzon syndrome mutation locks the receptor in a permanently on position.

As mouse embryos with the mutation grew, cells destined to become the palate initially grew faster than normal cells, as anticipated. But just before palate formation, the growth of these cells lagged behind their normal pace of proliferation. That was unexpected because the signals created by mutant FGFR2 should logically have maintained an increased rate of cell proliferation in the palate, Ornitz indicates.

In a normal mouse embryo, groups of cells called the palatal shelf on either side of the mouth grow outward, elevate to meet in the middle and fuse to form the palate. But in the mutant mice embryos, the stunted growth of this tissue prevented the palatal shelves from properly elevating, meeting and fusing. In addition, the researchers detected a decrease in some key components of the supporting matrix between cells of the palate.

Another of the study's coauthors, Kai Yu, Ph.D., a scientist in the Ornitz lab, created genetically engineered mice in which FGF receptors were inactivated in tissue that gives rise to the palate. These mice also developed cleft palate.

In palate cells grown in the lab, the researchers looked at the FGF cell-signaling network, in which FGFR2 participates. They compared the effect of increased activity of FGF signaling with decreased activity of the same network, and interestingly, both led to cleft palate.

"We found that overactivation of an important signaling pathway resulted in loss of function," Snyder-Warwick says. "Our results suggest a different way of thinking about mutations in the FGF signaling network. This study clearly showed that this FGF signaling pathway is a critical regulator of palate development."

These findings strengthen the evidence that the developmental processes in which FGFR2 is involved could be targeted with drugs in order to ensure normal palate growth.

"It's possible that someday doctors might be able to administer drugs that would either slightly activate or slightly inhibit FGFR2 function," Ornitz says. "That might be enough to tip the balance from a cleft palate to a normal palate during embryonic development."


'/>"/>

Contact: Gwen Ericson
ericsong@wustl.edu
314-286-0141
Washington University in St. Louis
Source:Eurekalert

Related medicine news :

1. High pollution linked to poor lung function growth in children in Mexico City
2. Researchers develop long-lasting growth hormone
3. Expanding Prevalent Population Will Drive Dramatic Growth for the Asthma Drug Market in China
4. Plexus Systems Ranks in Top Third of the 2007 Inc. 5,000 with Three-Year Sales Growth of 226%
5. Neusoft Becomes First Global Growth Company Partner of World Economic Forum
6. AWT Management Announce Aggressive Growth and Acquisition Strategy
7. Cynosure to Present at the Maxim Group Growth Conference
8. Human C-reactive protein regulates myeloma tumor cell growth and survival
9. Sangamo BioSciences to Present at the ThinkEquity Partners Growth Conference
10. Cepheid to Present at ThinkEquity Partners 5th Annual Growth Conference
11. Spectranetics to Present at The A.G Edwards Growth Conference on September 18
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... ... June 25, 2016 , ... The temporary closing of Bruton Memorial Library on June ... , brings up a new, often overlooked aspect of head lice: the parasite’s ability to ... is not a common occurrence, but a necessary one in the event that lice have ...
(Date:6/25/2016)... ... June 25, 2016 , ... ... non-athletes recover from injury. Recently, he has implemented orthobiologic procedures as a method ... —Johnson is one of the first doctors to perform the treatment. Orthobiologics are ...
(Date:6/24/2016)... ... , ... Those who have experienced traumatic events may suffer from a complex ... as drug or alcohol abuse, as a coping mechanism. To avoid this pain and ... a traumatic event. , Trauma sufferers tend to feel a range of emotions, from ...
(Date:6/24/2016)... , ... June 24, 2016 , ... Global law firm ... 2016 Legal Elite. The attorneys chosen by their peers for this recognition are considered ... Seven Greenberg Traurig Shareholders received special honors as members of this year’s Legal Elite ...
(Date:6/24/2016)... ... June 24, 2016 , ... People across the U.S. are ... Code Talker Award, an essay contest in which patients and their families pay tribute ... presented at the 2016 National Society of Genetic Counselors (NSGC) Annual Education Conference (AEC) ...
Breaking Medicine News(10 mins):
(Date:6/26/2016)... , June 26, 2016 ... care operating models within the health care industry is ... financial efficiency , Deloitte offers a suite of ... business issues impacting efficient cost optimization: labor resource analysis, ... These services facilitate better outcomes and better economics ...
(Date:6/24/2016)... , June 24, 2016 ... Markets has announced the addition of the " ... offering. This ... and provides an updated review, including its applications in ... the total market, which includes three main industries: pharmaceutical ...
(Date:6/24/2016)... , June 24, 2016 Research ... World Market for Companion Diagnostic Tests" report to their ... Market for Companion Diagnostics The World Market ... and personalized medicine diagnostics. Market analysis in the report includes ... Test Market (In Vitro Diagnostic Kits) by Region (N. America, ...
Breaking Medicine Technology: