Liver development: Lessons from knockout mice and mutant fish

The liver is an organ with vital functions, including the processing and storage of nutrients, maintenance of serum composition, detoxification and bile production. Over the last 10years, there have been major advances in our understanding of the molecular and cellular mechanisms underlying liver development. These advances have been achieved through the use of knockout mice as well as through forward-genetics studies employing mutant fish. The examination of many such murine and piscine mutants with defects in liver formation and/or function have pinpointed numerous factors crucial for hepatic cell differentiation and growth. In addition, these studies have permitted the identification of several important liver-specific markers that allow the contributions of variouscell types to hepatogenesis to be monitored. This review summarizes our current state of knowledge of the shared molecular mechanisms that underlie liver development in species as diverse as fish and mice. A better molecular understanding of liver formation may provide new insights into both normal liver biology and liver disease.