Low wnt/β-catenin signaling determines leaky vessels in the subfornical organ and affects water homeostasis in mice
The circumventricular organs (CVOs) in the central nervous system (CNS) lack a vascular blood-brain barrier (BBB), creating communication sites for sensory or secretory neurons, involved in body homeostasis. Wnt/β-catenin signaling is essential for BBB development and maintenance in endothelial cell...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/43818 |
| _version_ | 1828221774630748160 |
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| author | Fabienne Benz Viraya Wichitnaowarat Martin Lehmann Raoul FV Germano Diana Mihova Jadranka Macas Ralf H Adams M Mark Taketo Karl-Heinz Plate Sylvaine Guérit Benoit Vanhollebeke Stefan Liebner |
| author_facet | Fabienne Benz Viraya Wichitnaowarat Martin Lehmann Raoul FV Germano Diana Mihova Jadranka Macas Ralf H Adams M Mark Taketo Karl-Heinz Plate Sylvaine Guérit Benoit Vanhollebeke Stefan Liebner |
| author_sort | Fabienne Benz |
| collection | DOAJ |
| description | The circumventricular organs (CVOs) in the central nervous system (CNS) lack a vascular blood-brain barrier (BBB), creating communication sites for sensory or secretory neurons, involved in body homeostasis. Wnt/β-catenin signaling is essential for BBB development and maintenance in endothelial cells (ECs) in most CNS vessels. Here we show that in mouse development, as well as in adult mouse and zebrafish, CVO ECs rendered Wnt-reporter negative, suggesting low level pathway activity. Characterization of the subfornical organ (SFO) vasculature revealed heterogenous claudin-5 (Cldn5) and Plvap/Meca32 expression indicative for tight and leaky vessels, respectively. Dominant, EC-specific β-catenin transcription in mice, converted phenotypically leaky into BBB-like vessels, by augmenting Cldn5+vessels, stabilizing junctions and by reducing Plvap/Meca32+ and fenestrated vessels, resulting in decreased tracer permeability. Endothelial tightening augmented neuronal activity in the SFO of water restricted mice. Hence, regulating the SFO vessel barrier may influence neuronal function in the context of water homeostasis. |
| first_indexed | 2024-04-12T16:45:14Z |
| format | Article |
| id | doaj.art-6bb1f0b34cc041bb9dafe0b26f55f9f9 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:45:14Z |
| publishDate | 2019-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-6bb1f0b34cc041bb9dafe0b26f55f9f92022-12-22T03:24:36ZengeLife Sciences Publications LtdeLife2050-084X2019-04-01810.7554/eLife.43818Low wnt/β-catenin signaling determines leaky vessels in the subfornical organ and affects water homeostasis in miceFabienne Benz0https://orcid.org/0000-0002-1891-7680Viraya Wichitnaowarat1Martin Lehmann2Raoul FV Germano3https://orcid.org/0000-0002-1247-0689Diana Mihova4Jadranka Macas5https://orcid.org/0000-0002-1661-2525Ralf H Adams6https://orcid.org/0000-0003-3031-7677M Mark Taketo7Karl-Heinz Plate8Sylvaine Guérit9Benoit Vanhollebeke10https://orcid.org/0000-0002-0353-365XStefan Liebner11https://orcid.org/0000-0002-4656-2258Institute of Neurology (Edinger Institute), University Hospital, Goethe University Frankfurt, Frankfurt am Main, GermanyInstitute of Neurology (Edinger Institute), University Hospital, Goethe University Frankfurt, Frankfurt am Main, GermanyInstitute of Neurology (Edinger Institute), University Hospital, Goethe University Frankfurt, Frankfurt am Main, GermanyLaboratory of Neurovascular Signaling, Department of Molecular Biology, ULB Neuroscience Institute, Université libre de Bruxelles, Bruxelles, BelgiumInstitute of Neurology (Edinger Institute), University Hospital, Goethe University Frankfurt, Frankfurt am Main, GermanyInstitute of Neurology (Edinger Institute), University Hospital, Goethe University Frankfurt, Frankfurt am Main, GermanyDepartment of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine, University of Münster, Faculty of Medicine, Münster, GermanyDivision of Experimental Therapeutics, Graduate School of Medicine, Kyoto University, Kyoto, JapanInstitute of Neurology (Edinger Institute), University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany; Excellence Cluster Cardio-Pulmonary systems (ECCPS), Partner site Frankfurt, Frankfurt, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Frankfurt, Germany; German Center for Cardiovascular Research (DZHK), Partner site Frankfurt/Mainz, Frankfurt, Germany; German Cancer Research Center (DKFZ), Heidelberg, GermanyInstitute of Neurology (Edinger Institute), University Hospital, Goethe University Frankfurt, Frankfurt am Main, GermanyLaboratory of Neurovascular Signaling, Department of Molecular Biology, ULB Neuroscience Institute, Université libre de Bruxelles, Bruxelles, Belgium; Walloon Excellence in Life Sciences and Biotechnology (WELBIO), Wallonia, BelgiumInstitute of Neurology (Edinger Institute), University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany; Excellence Cluster Cardio-Pulmonary systems (ECCPS), Partner site Frankfurt, Frankfurt, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Frankfurt, GermanyThe circumventricular organs (CVOs) in the central nervous system (CNS) lack a vascular blood-brain barrier (BBB), creating communication sites for sensory or secretory neurons, involved in body homeostasis. Wnt/β-catenin signaling is essential for BBB development and maintenance in endothelial cells (ECs) in most CNS vessels. Here we show that in mouse development, as well as in adult mouse and zebrafish, CVO ECs rendered Wnt-reporter negative, suggesting low level pathway activity. Characterization of the subfornical organ (SFO) vasculature revealed heterogenous claudin-5 (Cldn5) and Plvap/Meca32 expression indicative for tight and leaky vessels, respectively. Dominant, EC-specific β-catenin transcription in mice, converted phenotypically leaky into BBB-like vessels, by augmenting Cldn5+vessels, stabilizing junctions and by reducing Plvap/Meca32+ and fenestrated vessels, resulting in decreased tracer permeability. Endothelial tightening augmented neuronal activity in the SFO of water restricted mice. Hence, regulating the SFO vessel barrier may influence neuronal function in the context of water homeostasis.https://elifesciences.org/articles/43818circumventricular organssubfornical organbeta-cateninblood-brain barrierWntwater homeostasis |
| spellingShingle | Fabienne Benz Viraya Wichitnaowarat Martin Lehmann Raoul FV Germano Diana Mihova Jadranka Macas Ralf H Adams M Mark Taketo Karl-Heinz Plate Sylvaine Guérit Benoit Vanhollebeke Stefan Liebner Low wnt/β-catenin signaling determines leaky vessels in the subfornical organ and affects water homeostasis in mice eLife circumventricular organs subfornical organ beta-catenin blood-brain barrier Wnt water homeostasis |
| title | Low wnt/β-catenin signaling determines leaky vessels in the subfornical organ and affects water homeostasis in mice |
| title_full | Low wnt/β-catenin signaling determines leaky vessels in the subfornical organ and affects water homeostasis in mice |
| title_fullStr | Low wnt/β-catenin signaling determines leaky vessels in the subfornical organ and affects water homeostasis in mice |
| title_full_unstemmed | Low wnt/β-catenin signaling determines leaky vessels in the subfornical organ and affects water homeostasis in mice |
| title_short | Low wnt/β-catenin signaling determines leaky vessels in the subfornical organ and affects water homeostasis in mice |
| title_sort | low wnt β catenin signaling determines leaky vessels in the subfornical organ and affects water homeostasis in mice |
| topic | circumventricular organs subfornical organ beta-catenin blood-brain barrier Wnt water homeostasis |
| url | https://elifesciences.org/articles/43818 |
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