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

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

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