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Publication : The Angiocrine Factor Rspondin3 Is a Key Determinant of Liver Zonation.

First Author  Rocha AS Year  2015
Journal  Cell Rep Volume  13
Issue  9 Pages  1757-64
PubMed ID  26655896 Mgi Jnum  J:259735
Mgi Id  MGI:6148104 Doi  10.1016/j.celrep.2015.10.049
Citation  Rocha AS, et al. (2015) The Angiocrine Factor Rspondin3 Is a Key Determinant of Liver Zonation. Cell Rep 13(9):1757-64
abstractText  Liver zonation, the spatial separation of different metabolic pathways along the liver sinusoids, is fundamental for proper functioning of this organ, and its disruption can lead to the development of metabolic disorders such as hyperammonemia. Metabolic zonation involves the induction of beta-catenin signaling around the central veins, but how this patterned activity is established and maintained is unclear. Here, we show that the signaling molecule Rspondin3 is specifically expressed within the endothelial compartment of the central vein. Conditional deletion of Rspo3 in mice disrupts activation of central fate, demonstrating its crucial role in determining and maintaining beta-catenin-dependent zonation. Moreover, ectopic expression of Rspo1, a close family member of Rspo3, induces the expression of pericentral markers, demonstrating Rspondins to be sufficient to imprint a more central fate. Thus, Rspo3 is a key angiocrine factor that controls metabolic zonation of liver hepatocytes.
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