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USC researchers identify alternate pathway that leads to palate development
Date:8/11/2008

alate, such as drugs, smoking and alcohol," Chai says.

Smad4 is one of the main signaling molecules used in the TGF- pathway during palate and tooth development. Chai says his team had initially hypothesized that since irregularities in the TGF- 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- 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 di
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Contact: Angelica Urquijo
urquijo@usc.edu
213-740-6568
University of Southern California
Source:Eurekalert

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