Zonal gene expression in murine liver: lessons from tumors.
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 beta-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 beta-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.
Institute of Pharmacology and Toxicology, Department of Toxicology, University of Tuebingen, Germany.
Stephan
S
Hailfinger
Maike
M
Jaworski
Albert
A
Braeuning
Albrecht
A
Buchmann
Michael
M
Schwarz
D000818:Animals; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D005974:Glutamate-Ammonia Ligase / Q000235:genetics; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D023421:Models, Animal; D015398:Signal Transduction; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics*
C495267:CTNNB1 protein, mouse; D015820:Cadherins; D051176:beta Catenin; D005974:Glutamate-Ammonia Ligase