Format

Send to

Choose Destination
Cell Rep. 2015 Dec 1;13(9):1757-64. doi: 10.1016/j.celrep.2015.10.049. Epub 2015 Nov 19.

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

Author information

1
Institute of Biology Valrose, Université de Nice-Sophia, 06108 Nice, France; Inserm, UMR1091, 06108 Nice, France; CNRS, UMR7277, 06108 Nice, France. Electronic address: rocha@unice.fr.
2
Institute of Biology Valrose, Université de Nice-Sophia, 06108 Nice, France; Inserm, UMR1091, 06108 Nice, France; CNRS, UMR7277, 06108 Nice, France.
3
Institute of Biology Valrose, Université de Nice-Sophia, 06108 Nice, France; Inserm, UMR1091, 06108 Nice, France; Plateforme PRISM, Institute of Biology Valrose, Université de Nice-Sophia, 06108 Nice, France.
4
MRC Human Genetics Unit, Western General Hospital Campus, Edinburgh, EH4 2XU Scotland, UK.
5
RIKEN Brain Science Institute, Saitama 351-0198, Japan.
6
Institute of Biology Valrose, Université de Nice-Sophia, 06108 Nice, France; Inserm, UMR1091, 06108 Nice, France; CNRS, UMR7277, 06108 Nice, France. Electronic address: andreas.schedl@unice.fr.

Abstract

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 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.

PMID:
26655896
DOI:
10.1016/j.celrep.2015.10.049
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center