| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2039106 | Cell Reports | 2015 | 8 Pages |
•Rspo3 is specifically expressed in central vein endothelial cells of the liver•Rspo3 is required to maintain metabolic zonation of the liver•Ectopic expression of Rspo1 is sufficient to convert hepatocytes to a central fate
SummaryLiver 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 β-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 β-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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