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Fig. 1 | BMC Systems Biology

Fig. 1

From: Paracrine and autocrine regulation of gene expression by Wnt-inhibitor Dickkopf in wild-type and mutant hepatocytes

Fig. 1

Simplified scheme of liver architecture and Wnt/ β-catenin signalling. a: The human liver is composed of two lobes of unequal size. It is supplied with blood from two sources, the hepatic portal vein and the hepatic arteries. The blood is distributed into capillaries that enter the liver lobules, which are hexagonal substructures that form the functional units of the liver. The blood flows through the sinusoids of the lobules from the portal vein (PV) to the central vein (CV). Hepatocytes surround the sinusoids separated by space of Disse. Typically, 15 to 25 hepatocytes align along the porto-central axis. b: The central component of the Wnt/ β-catenin signalling pathway is β-catenin (purple). β-Catenin is constantly produced and degraded and maintains a low expression level. The degradation is predominantly mediated by a destruction complex comprising APC (grey), Axin and the kinase GSK. Upon stimulation by Wnt ligands (grey), the Wnt receptor complex activates intracellular proteins including Dishevelled (Dsh) that induce a partial inactivation of the destruction complex. In consequence, β-catenin degradation is impaired and more β-catenin can translocate into the nucleus. There, it binds to transcriptional regulators of the TCF family and co-regulates the expression of target genes. In particular, β-catenin/TCF complexes induce the expression of Dkk (green). Dkk is secreted by the cells and acts as an inhibitor of the pathway by competing with Wnt for receptor binding. The colours highlighting Wnt, APC, β-catenin, target genes and Dkk correspond to the colour code used throughout the manuscript

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