DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for Alagille syndrome
Organ function depends on tissues adopting the correct architecture. However, insights into organ architecture are currently hampered by an absence of standardized quantitative 3D analysis. We aimed to develop a robust technology to visualize, digitalize, and segment the architecture of two tubular...
Main Authors: | , , , , , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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eLife Sciences Publications Ltd
2021-02-01
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Series: | eLife |
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Online Access: | https://elifesciences.org/articles/60916 |
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author | Simona Hankeova Jakub Salplachta Tomas Zikmund Michaela Kavkova Noémi Van Hul Adam Brinek Veronika Smekalova Jakub Laznovsky Feven Dawit Josef Jaros Vítězslav Bryja Urban Lendahl Ewa Ellis Antal Nemeth Björn Fischler Edouard Hannezo Jozef Kaiser Emma Rachel Andersson |
author_facet | Simona Hankeova Jakub Salplachta Tomas Zikmund Michaela Kavkova Noémi Van Hul Adam Brinek Veronika Smekalova Jakub Laznovsky Feven Dawit Josef Jaros Vítězslav Bryja Urban Lendahl Ewa Ellis Antal Nemeth Björn Fischler Edouard Hannezo Jozef Kaiser Emma Rachel Andersson |
author_sort | Simona Hankeova |
collection | DOAJ |
description | Organ function depends on tissues adopting the correct architecture. However, insights into organ architecture are currently hampered by an absence of standardized quantitative 3D analysis. We aimed to develop a robust technology to visualize, digitalize, and segment the architecture of two tubular systems in 3D: double resin casting micro computed tomography (DUCT). As proof of principle, we applied DUCT to a mouse model for Alagille syndrome (Jag1Ndr/Ndr mice), characterized by intrahepatic bile duct paucity, that can spontaneously generate a biliary system in adulthood. DUCT identified increased central biliary branching and peripheral bile duct tortuosity as two compensatory processes occurring in distinct regions of Jag1Ndr/Ndr liver, leading to full reconstitution of wild-type biliary volume and phenotypic recovery. DUCT is thus a powerful new technology for 3D analysis, which can reveal novel phenotypes and provide a standardized method of defining liver architecture in mouse models. |
first_indexed | 2024-04-11T10:34:51Z |
format | Article |
id | doaj.art-b15a162506be45549627228691187bdb |
institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-11T10:34:51Z |
publishDate | 2021-02-01 |
publisher | eLife Sciences Publications Ltd |
record_format | Article |
series | eLife |
spelling | doaj.art-b15a162506be45549627228691187bdb2022-12-22T04:29:19ZengeLife Sciences Publications LtdeLife2050-084X2021-02-011010.7554/eLife.60916DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for Alagille syndromeSimona Hankeova0https://orcid.org/0000-0002-7797-3818Jakub Salplachta1https://orcid.org/0000-0002-0149-7843Tomas Zikmund2Michaela Kavkova3Noémi Van Hul4https://orcid.org/0000-0003-1410-8808Adam Brinek5Veronika Smekalova6Jakub Laznovsky7Feven Dawit8Josef Jaros9Vítězslav Bryja10https://orcid.org/0000-0002-9136-5085Urban Lendahl11Ewa Ellis12https://orcid.org/0000-0002-3057-5337Antal Nemeth13Björn Fischler14Edouard Hannezo15https://orcid.org/0000-0001-6005-1561Jozef Kaiser16Emma Rachel Andersson17https://orcid.org/0000-0002-8608-625XDepartment of Biosciences and Nutrition, Karolinska Institutet, Solna, Sweden; Department of Experimental Biology, Masaryk University, Brno, Czech RepublicCEITEC – Central European Institute of Technology, Brno University of Technology, Brno, Czech RepublicCEITEC – Central European Institute of Technology, Brno University of Technology, Brno, Czech RepublicCEITEC – Central European Institute of Technology, Brno University of Technology, Brno, Czech RepublicDepartment of Biosciences and Nutrition, Karolinska Institutet, Solna, SwedenCEITEC – Central European Institute of Technology, Brno University of Technology, Brno, Czech RepublicCEITEC – Central European Institute of Technology, Brno University of Technology, Brno, Czech RepublicCEITEC – Central European Institute of Technology, Brno University of Technology, Brno, Czech RepublicDepartment of Pediatrics, Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Karolinska University Hospital, Solna, SwedenDepartment of Histology and Embryology, Masaryk University, Brno, Czech RepublicDepartment of Experimental Biology, Masaryk University, Brno, Czech RepublicDepartment of Cell and Molecular Biology, Karolinska Institutet, Solna, SwedenDepartment of Pediatrics, Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Karolinska University Hospital, Solna, SwedenDepartment of Laboratory Medicine, Karolinska Institutet, Solna, SwedenDepartment of Pediatrics, Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Karolinska University Hospital, Solna, SwedenInstitute of Science and Technology, Klosterneuburg, AustriaCEITEC – Central European Institute of Technology, Brno University of Technology, Brno, Czech RepublicDepartment of Biosciences and Nutrition, Karolinska Institutet, Solna, Sweden; Department of Cell and Molecular Biology, Karolinska Institutet, Solna, SwedenOrgan function depends on tissues adopting the correct architecture. However, insights into organ architecture are currently hampered by an absence of standardized quantitative 3D analysis. We aimed to develop a robust technology to visualize, digitalize, and segment the architecture of two tubular systems in 3D: double resin casting micro computed tomography (DUCT). As proof of principle, we applied DUCT to a mouse model for Alagille syndrome (Jag1Ndr/Ndr mice), characterized by intrahepatic bile duct paucity, that can spontaneously generate a biliary system in adulthood. DUCT identified increased central biliary branching and peripheral bile duct tortuosity as two compensatory processes occurring in distinct regions of Jag1Ndr/Ndr liver, leading to full reconstitution of wild-type biliary volume and phenotypic recovery. DUCT is thus a powerful new technology for 3D analysis, which can reveal novel phenotypes and provide a standardized method of defining liver architecture in mouse models.https://elifesciences.org/articles/60916Alagille syndromecholangiopathyvasculatureMicroCTresin |
spellingShingle | Simona Hankeova Jakub Salplachta Tomas Zikmund Michaela Kavkova Noémi Van Hul Adam Brinek Veronika Smekalova Jakub Laznovsky Feven Dawit Josef Jaros Vítězslav Bryja Urban Lendahl Ewa Ellis Antal Nemeth Björn Fischler Edouard Hannezo Jozef Kaiser Emma Rachel Andersson DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for Alagille syndrome eLife Alagille syndrome cholangiopathy vasculature MicroCT resin |
title | DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for Alagille syndrome |
title_full | DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for Alagille syndrome |
title_fullStr | DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for Alagille syndrome |
title_full_unstemmed | DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for Alagille syndrome |
title_short | DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for Alagille syndrome |
title_sort | duct reveals architectural mechanisms contributing to bile duct recovery in a mouse model for alagille syndrome |
topic | Alagille syndrome cholangiopathy vasculature MicroCT resin |
url | https://elifesciences.org/articles/60916 |
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