Researchers at Brown University have identified the primary signals that tell an embryo where and when a liver should appear and have used those signals to direct immature mouse cells to become liver cells and begin liver formation.

Understanding how to control both tissue growth and cell identity may lead to new disease-fighting methods that would rely on tissue regeneration and the ability to reprogram diseased cells into normal ones.

"This basic research won't translate into a cure tomorrow, but opens the way to think about new mechanisms of dealing with certain tissue degenerative diseases, particularly of the liver," said Ken Zaret, professor of molecular biology, cell biology and biochemistry in the Brown School of Medicine. "The liver is a critical organ and a target for viral hepatitis, alcoholism, metabolic diseases and cancer."

The experiments were conducted using undifferentiated cells, called endoderm cells, removed from the inner layer of mouse embryos. In the developing mouse, these endoderm cells have the potential to become a liver, pancreas, or other gut organs, based on the signals received.

In the June 18 issue of Science, Zaret and colleagues describe the signaling mechanisms that initiate these unspecialized embryonic cells to begin liver formation. The researchers developed the techniques to sift through tiny fragments of tissue to identify the relevant signaling factors. In doing so, they found that the growth factors FGF1 and FGF2, and to some extent FGF8, begin the liver development process by differentiating the multi-potential endoderm cells into liver cells. FGF8 also helps prompt the cells to begin growing and forming liver tissue.

"Three signals are being conveyed to make sure that the liver appears at a specific time and place," Zare
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Contact: Scott Turner
Scott_Turner@Brown.edu
401-863-1862
Brown University
18-Jun-1999