The Angiocrine Factor Rspondin3 Is a Key Determinant of Liver Zonation
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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-12-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715012383 |
| _version_ | 1819078454669213696 |
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| author | Ana Sofia Rocha Valerie Vidal Marjolijn Mertz Timothy J. Kendall Aurelie Charlet Hitoshi Okamoto Andreas Schedl |
| author_facet | Ana Sofia Rocha Valerie Vidal Marjolijn Mertz Timothy J. Kendall Aurelie Charlet Hitoshi Okamoto Andreas Schedl |
| author_sort | Ana Sofia Rocha |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T19:13:21Z |
| format | Article |
| id | doaj.art-3e027cb5dce345af9dea4f0ceda8821c |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T19:13:21Z |
| publishDate | 2015-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-3e027cb5dce345af9dea4f0ceda8821c2022-12-21T18:53:08ZengElsevierCell Reports2211-12472015-12-011391757176410.1016/j.celrep.2015.10.049The Angiocrine Factor Rspondin3 Is a Key Determinant of Liver ZonationAna Sofia Rocha0Valerie Vidal1Marjolijn Mertz2Timothy J. Kendall3Aurelie Charlet4Hitoshi Okamoto5Andreas Schedl6Institute of Biology Valrose, Université de Nice-Sophia, 06108 Nice, FranceInstitute of Biology Valrose, Université de Nice-Sophia, 06108 Nice, FranceInstitute of Biology Valrose, Université de Nice-Sophia, 06108 Nice, FranceMRC Human Genetics Unit, Western General Hospital Campus, Edinburgh, EH4 2XU Scotland, UKInstitute of Biology Valrose, Université de Nice-Sophia, 06108 Nice, FranceRIKEN Brain Science Institute, Saitama 351-0198, JapanInstitute of Biology Valrose, Université de Nice-Sophia, 06108 Nice, FranceLiver 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.http://www.sciencedirect.com/science/article/pii/S2211124715012383 |
| spellingShingle | Ana Sofia Rocha Valerie Vidal Marjolijn Mertz Timothy J. Kendall Aurelie Charlet Hitoshi Okamoto Andreas Schedl The Angiocrine Factor Rspondin3 Is a Key Determinant of Liver Zonation Cell Reports |
| title | The Angiocrine Factor Rspondin3 Is a Key Determinant of Liver Zonation |
| title_full | The Angiocrine Factor Rspondin3 Is a Key Determinant of Liver Zonation |
| title_fullStr | The Angiocrine Factor Rspondin3 Is a Key Determinant of Liver Zonation |
| title_full_unstemmed | The Angiocrine Factor Rspondin3 Is a Key Determinant of Liver Zonation |
| title_short | The Angiocrine Factor Rspondin3 Is a Key Determinant of Liver Zonation |
| title_sort | angiocrine factor rspondin3 is a key determinant of liver zonation |
| url | http://www.sciencedirect.com/science/article/pii/S2211124715012383 |
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