Gene trigger for pancreas formation identified

Before the pancreas is a pancreas, it is just two tiny bumps--two groups of cells sprouting from a central tube. What makes these cells bud off from the main group? How do they go on to make all the cell types of the mature pancreas? These are the kinds of questions that drive the research efforts of Vanderbilt developmental biologist Chris Wright and colleagues. The answers could pave the way toward limitless supplies of pancreatic cells for transplantation therapy of diabetes.

"It has been established that islet cell transplantation can solve the diabetes problem," said Wright, referring to studies carried out in Edmonton, Canada and elsewhere. "The problem is having a suitable and sufficient source of transplantation material."

Donated pancreases and the technical expertise required to isolate functioning islet cells--the pancreatic cells that produce insulin--will not meet the demand, Wright said. An alternative, he said, is to produce insulin-secreting cells from embryonic or other stem cells.

"If we can identify the factors that determine pancreatic cell fate," he said, "we might be able to coerce embryonic stem cells or other cells to turn into pancreas."

One of these factors is a gene called PTF1p48 (p48 for short). Wright and colleagues reported in Nature Genetics, published online August 19, that p48 is required for the development of the pancreas, both its exocrine cells--those that secrete digestive enzymes--and its endocrine cells--those that secrete insulin and other hormones.

Wright's team used what one reviewer of the paper called "a novel and powerful cell marking method" to track cells in the mouse that express the p48 gene, starting very early in embryonic pancreas formation. The method relied on genetic manipulations to introduce an inherited marker--a blue color that could be followed in cells that turned on the p48 gene, and in all the cells that came from those cells.

A simple way to thin

Contact: John Howser
Vanderbilt University Medical Center

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