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Mount Sinai researchers find mechanism behind cleft palate development

2010-09-15
(Press-News.org) Researchers from Mount Sinai School of Medicine have found a new mechanism that explains why a certain gene mutation causes craniofrontonasal syndrome (CFNS), a disorder that causes cleft palate and other malformations in the face, brain, and skeleton. Cleft palate affects one of every 1,000 newborns. The research is published in the September 15 issue of Genes & Development.

Previous research has shown that a mutation in a gene called ephrin-B1 caused abnormalities in facial development, but researchers were uncertain of how. Philipe M. Soriano, PhD, Professor, Developmental and Regenerative Biology, and Jeffrey O. Bush, PhD, Postdoctoral Fellow, Developmental and Regenerative Biology, both at Mount Sinai School of Medicine, studied mice embryos that were genetically engineered to have a mutation in the ephrin-B1 gene. They determined that ephrin-B1 controls craniofacial development by signaling cells to multiply. When there is a mutation in this gene, it causes anomalies in the cell proliferation process.

"Common thinking has been that ephrin-B1 only guided cells in craniofacial development," said Dr. Soriano. "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."

Drs. Bush and Soriano also wanted to determine why females with one normal copy of the ephrin-B1 gene are more severely malformed than males who have no copy of the gene at all. They found that female mice embryos with this type of mutation had a so-called "mosaic" cell proliferation, meaning cell multiplication is disrupted in some areas while developing normally in others. This creates abnormal craniofacial development.

"Craniofacial anomalies are among the most common human birth defect," said Dr. Bush. "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."

Drs. Bush and Soriano plan to study ephrin-B1 further by identifying which molecules work in conjunction with it and how. Gaining a further understanding of the signaling mechanisms of this gene will likely lead to designing prevention and treatment strategies.

INFORMATION:

About The Mount Sinai Medical Center

The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of few medical schools embedded in a hospital in the United States. It has more than 3,400 faculty in 32 departments and 15 institutes, and ranks among the top 20 medical schools both in National Institute of Health funding and by U.S. News & World Report. The school received the 2009 Spencer Foreman Award for Outstanding Community Service from the Association of American Medical Colleges.

The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation's oldest, largest and most-respected voluntary hospitals. In 2009, U.S. News & World Report ranked The Mount Sinai Hospital among the nation's top 20 hospitals based on reputation, patient safety, and other patient-care factors. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 530,000 outpatient visits took place.

For more information, visit www.mountsinai.org. Follow us on Twitter @mountsinainyc.

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[Press-News.org] Mount Sinai researchers find mechanism behind cleft palate development