Researchers say they have identified a master regulator gene that determines whether an embryonic cell in mice becomes a pancreatic cell or biliary cell, in a discovery that could be a step toward a cure for type 1 diabetes. The scientists at Cincinnati Children's Hospital Medical Center say they’ve fingered Sox17 as the protein that controls which genes are turned on or off in a cell, giving them hope that they can find a way to eventually coax stem cells into pancreatic cells. Type 1 diabetes develops when the immune system attacks insulin-producing beta cells in the pancreas, usually destroying them beyond repair before the illness is diagnosed.

­The research, which appears in the journal Developmental Cell, reveals that both the pancreas and the biliary system share a common cellular ancestry in the early mouse embryo. Previously, it was believed the origin of the biliary system, which is vital for digestion, was connected to early embryonic formation of the liver, the researchers say.

“We show that Sox17 acts like a toggle or binary switch that sets off a cascade of genetic events,” says James Wells, a researcher in the Division of Developmental Biology at Cincinnati Children’s Hospital and associate professor of pediatrics at the University of Cincinnati College of Medicine. “In normal embryonic development, when you have an undecided cell, if Sox17 goes one way the cell becomes part of the biliary system. If it goes the other way, the cell becomes part of the pancreas.”

As many as 3 million Americans may have type 1 diabetes and each year more than 15,000 children—40 per day—are diagnosed with the disease in the United States, according to the Juvenile Diabetes Research Foundation. Although insulin can help treat diabetes, there is no cure. Among the technologies being scrutinized are pancreatic cell transplantation and the development of an artificial pancreas that uses algorithms to provide the right amount of insulin for patients.

Cincinnati Children's researchers have been looking at how to guide embryonic stem cells to become pancreatic beta cells, which scientists believe could be used to treat or cure type 1 diabetes. "With this study showing us that turning one gene on or off in a mouse embryo instructs a cell to become pancreatic or biliary, now we'll see if that same gene, Sox17, can be used to direct an embryonic stem cell to become a biliary cell instead of a pancreatic cell,” says Wells. “This might be used one day to replace a diseased pancreas or bile duct in people.”

Sox17 may also turn on or off other genes, a possibility that Wells and his colleagues are investigating using the data from the current study.

“Although Sox17 is the master switch, it triggers a molecular cascade of switches, and a defect in any of those can cause the whole thing to go wrong, resulting in congenital defects of the pancreas and biliary system,” the researcher says.