Stephan Hailfinger and Maike Jaworski contributed equally to this work.
Liver Biology and Pathobiology
Zonal gene expression in murine liver: Lessons from tumors†
Article first published online: 22 FEB 2006
Copyright © 2006 American Association for the Study of Liver Diseases
Volume 43, Issue 3, pages 407–414, March 2006
How to Cite
Hailfinger, S., Jaworski, M., Braeuning, A., Buchmann, A. and Schwarz, M. (2006), Zonal gene expression in murine liver: Lessons from tumors. Hepatology, 43: 407–414. doi: 10.1002/hep.21082
Potential conflict of interest: Nothing to report.
- Issue published online: 22 FEB 2006
- Article first published online: 22 FEB 2006
- Manuscript Accepted: 22 DEC 2005
- Manuscript Received: 25 OCT 2005
- Deutsche Forschungsgemeinschaft. Grant Number: SCHW 329/3-2
- Deutsche Krebshilfe. Grant Number: 106356
Gene expression in hepatocytes within the liver lobule is differentially regulated along the portal to central axis; however, the mechanisms governing the processes of zonation within the lobule are unknown. A model for zonal heterogeneity in normal liver is proposed, based on observations of differential expression of genes in liver tumors from mice that harbor activating mutations in either Catnb (which codes for β-catenin) or Ha-ras. According to the model, the regulatory control consists of two opposing signals, one delivered by endothelial cells of the central veins activating a β-catenin–dependent pathway (retrograde signal), the other by blood-borne molecules activating Ras-dependent downstream cascades (anterograde signal). In conclusion, gradients of opposing signaling molecules along the portocentral axis determine the pattern of enzymes and other proteins expressed in hepatocytes of the periportal and pericentral domains of the liver lobule. (HEPATOLOGY 2006;43:407–414.)