Molecular determinants of liver zonation.

The phenomenon of "liver zonation" is a remarkable process by which the liver fulfills its metabolic functions, involving highly dynamic transcriptional mechanisms. Its understanding is therefore a challenging issue. Zonation is reflected in heterogeneity of hepatocytes along the porto-central axis of the liver: periportal hepatocytes, located in the vicinity of the afferent portal vein, do not express the same metabolic enzymes than pericentral hepatocytes located near the efferent central vein. This is mainly dictated at the transcriptional level by specific pericentral versus periportal genetic programs. The mechanisms by which zonation is established have been extensively investigated since its initial discovery 40 years ago. The discovery in 2006 that Wnt/β-catenin pericentral signaling was a master regulator of this complex liver topology has been a major breakthrough. A major current priority in the field is the integration of the β-catenin pathway with other determinants that govern zonation of the liver.