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Solving the mystery of the dancer mice, and cleft lip too

ame easier."

Bush and colleagues did some homework on those 97 genes and discovered that one of the genes is Tbx10; that caught their interest, Bush says, because it encodes one of a family of proteins known to be crucial in development by turning on and off other genes. Two closely related genes are known to play a role in cranio-facial development, he says, and mutations in other "T-box" genes result in birth defects.

Looking more closely, the team found the precise genetic defect responsible for the Dancer mice: They discovered a chunk of genetic material from another gene a specialized strip of DNA responsible for turning a gene on embedded into the DNA of the Tbx10 gene. They found that in mice with the Dancer mutation, the Tbx10 gene is active in places it's normally not, including the developing face.

While the team is investigating exactly how Tbx10 contributes to cleft lip and palate, Jiang suspects there are at least 10 genes linked to the disorder. Previously a gene in mice was linked to some cases of cleft palate, and then scientists found a similar gene in humans but still the cause of most cases of cleft lip and palate in humans is not known.

"It's likely that mutations in many different genes could cause clefting," says Jiang. "Now that we've identified one specific mutation, we will investigate the molecular networks that control facial development to look for other important players in the clefting process."

Going from a few cells of an embryo to a full-fledged face whether human or mouse requires the cooperation of hundreds of genes turning on or off at just the right time, Jiang says.

"The face develops initially from five separate parts surrounding the oral cavity hundreds of genes are involved in bringing the parts together to form the intact face. The development of the face has been under-studied in biology. It's a complex problem," says Jiang, an assistant professor of Biomedical Gen
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Contact: Tom Rickey
trickey@admin.rochester.edu
585-275-7954
University of Rochester Medical Center
30-Apr-2004


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