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Determining The Fate Of Cells In The Human Body

A study in the April issue (currently available online) of Nature Genetics establishes a model that may take scientists closer to understanding how cells in the human body determine their own fate.

Researchers, led by Anthony Firulli, Ph.D., associate professor of pediatrics and of medical and molecular genetics at the Indiana University School of Medicine, investigated the interaction of proteins responsible for Saethre-Chotzen Syndrome, a rare genetic disorder associated with limb abnormalities including webbed fingers and other developmental defects.

In the study, Dr. Firulli and colleagues studied how two proteins, Twist1 and Hand2, which are antagonists, couple to determine the number of digits on a hand, paw or wing, and whether these digits are webbed or not. In addition to limb abnormalities, these proteins are associated with cardiac and placental tissue defects. Twist1 mutations are encountered at high frequency in patients with Saethre-Chotzen Syndrome.

"By studying a disease in which things go wrong at the cellular level, we gain insight into how to correct these errors," said Dr. Firulli, who also is a molecular biologist at the medical school's Herman B Wells Center for Pediatric Research.

"From a pediatrics perspective -- there are many congenital defects - holes in the heart, cleft pallet, webbed hands -- which are outcomes of inappropriate molecular programs due to miscommunication at the cellular level. If we can understand what is going wrong, we may be able to correct these problems before birth," said Dr. Firulli.

Co-authors of the study are IU School of Medicine investigators Beth A. Firulli, Dayana Krawchuk, Victoria E. Centonze, Neil Vargesson, David M. Virshup, Simon J. Conway, Peter Cserjesi and Columbia University's Ed Laufer.

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The study was funded by the National Heart, Lung and Blood Institute and the March of Dimes. Dr. Laufer's work is supported by the Howard Hughes Medical Inst
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Source:Indiana University School Of Medicine


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