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Zonal gene expression in murine liver: Lessons from tumors

✍ Scribed by Stephan Hailfinger; Maike Jaworski; Albert Braeuning; Albrecht Buchmann; Michael Schwarz

Publisher: John Wiley and Sons
Year: 2006
Tongue: English
Weight: 438 KB
Volume: 43
Category: Article
ISSN: 0270-9139
DOI: 10.1002/hep.21082

No coin nor oath required. For personal study only.

✦ Synopsis

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 ␤-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 ␤-catenindependent 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.

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