Liver development and cancer formation in zebrafish

Birth Defects Res C Embryo Today. 2011 Jun;93(2):157-72. doi: 10.1002/bdrc.20205.

Abstract

Liver is the largest organ in the human body, and it regulates many physiological processes. Many studies on liver development in different model organisms have demonstrated that the mechanism of hepatogenesis is conserved in vertebrates. The identification of the genes and regulatory pathways involved in liver formation provides a basis for the diagnosis of liver diseases and therapeutic interventions. Hepatocellular carcinoma is the third leading cause of mortality worldwide. In the last decade, genetic alterations, which include the gain and loss of DNA, as well as mutations and epigenomic changes, have been identified as important factors in liver cancer. Many genetic pathways are dysregulated during carcinogenesis. Here, we review the gene regulatory networks that underlie liver organogenesis and the dysregulation of these pathways in liver cancer. The genes and pathways involved in hepatogenesis and liver cancer are largely conserved between zebrafish and humans, making this an ideal model organism for the study of this disease. A better understanding of liver development may aid in the development of new diagnostic and therapeutic approaches to liver cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Ankyrins / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / physiopathology
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Expression Regulation, Neoplastic / physiology
  • Gene Regulatory Networks / genetics*
  • Gene Regulatory Networks / physiology
  • Liver / embryology*
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / physiopathology
  • Models, Animal*
  • Morphogenesis / genetics*
  • Morphogenesis / physiology
  • Mutation / genetics
  • Retinoblastoma Protein / genetics
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Trans-Activators / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Viral Regulatory and Accessory Proteins
  • Wnt Proteins / metabolism
  • Zebrafish*
  • beta Catenin / metabolism

Substances

  • Ankyrins
  • Cyclin-Dependent Kinase Inhibitor p16
  • Retinoblastoma Protein
  • Trans-Activators
  • Tumor Suppressor Protein p53
  • Viral Regulatory and Accessory Proteins
  • Wnt Proteins
  • beta Catenin
  • hepatitis B virus X protein