Gene's role in cleft palate established

A key link between the human ephrin-B1 gene and cleft palate and other craniofacial anomalies associated with craniofrontonasal syndrome (CFNS) has been demonstrated by researchers at Mount Sinai School of Medicine, according to findings published in the September 15 issue of Genes & Development (Vol. 24:18, pp. 2068-2080). While previous research has established that mutation of the ephrin-B1 is the source of CFNS, it was unclear why.

Mice genetically engineered to have a mutatation in the ephrin-B1 gene were studied by Philipe Soriano, Ph.D., a professor of developmental and regenerative biology, and Jeffrey Bush, Ph.D., a postdoctoral fellow of developmental and regenerative biology, both at the Mount Sinai School of Medicine.

"Here we demonstrate that ephrin-B1 plays an intrinsic role in palatal shelf outgrowth in the mouse by regulating cell proliferation in the anterior palatal shelf mesenchyme," the authors wrote in the study.

"Common thinking has been that ephrin-B1 only guided cells in craniofacial development," Dr. Soriano said in a press release. "We were surprised to learn that, instead, this gene signals for cells to multiply, providing us with a clear understanding of why craniofacial development is abnormal when a mutation is present."

Females with a single normal copy of the gene, curiously, had more severe resulting mutation than males with none at all, a phenomenon the two doctors sought to explain. In such circumstances, a "mosaic" cell proliferation occurred where normal cell growth and disrupted cell growth took place simultaneously in female mice embryos.

"Craniofacial anomalies are among the most common human birth defect," Dr. Bush said in the press release. "Our findings represent a critical step forward in understanding how cleft palate and other malformations develop, and will hopefully bring us closer to finding ways to prevent or treat these abnormalities."

Future studies by Drs. Bush and Soriano will seek to identify which molecules work with ephrin-B1 to gain a deeper understanding of its signaling mechanisms.

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