Scientists Discover How Immature Cells Decide to Become a Liver

Release Date:
Alison Davis, NIGMS

Organs are complicated collections of cells that together perform important functions in the body. The liver, for example, plays a key role in processing and detoxifying foreign substances, which include everything from helpful medicines to dangerous poisons. Helping to control levels of blood sugar is yet another of the liver's important functions. Thus, the entire body is placed at serious risk when this organ becomes disabled by diseases such as hepatitis, alcoholism, or cancer. Scientists yearn to be able to decipher the master set of instructions that tells immature cells in the embryo how and when to mature and form one organ, but not another.

In an important first step toward unraveling some of these secrets, Dr. Ken Zaret and his coworkers at Brown University have discovered a class of related proteins that commit embryonic precursor cells to mature into liver cells. New studies show that at least three of these proteins, which are fibroblast growth factors called FGF1, FGF2, and FGF8, direct precursor cells that could become part of the lung, stomach, liver, thyroid, or pancreas to commit to becoming a liver cell. Cells in all of these organs share a common ancestor called a definitive endoderm cell, which itself traces back to the few cells that constitute the days-old embryo.

Understanding the body's decision-making process when it comes to forming organs from embryonic cells has implications for tissue regeneration--the process of rebuilding a diseased or damaged organ or tissue, or further into the future, for making new organs or tissues from scratch. Knowing how the body flips such genetic "switches" as the FGF signaling pathways will also aid scientists in understanding the origin of diseases that strike the liver as well as in developing means to treat those ailments.


Jung J, Zheng M, Goldfarb M, Zaret K. Initiation of mammalian liver development from endoderm by fibroblast growth factors. Science 1999;284:1998-2003.

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