Svep1 is a binding ligand of Tie1 and affects specific aspects of facial lymphatic development in a Vegfc-independent manner
Multiple factors are required to form functional lymphatic vessels. Here, we uncover an essential role for the secreted protein Svep1 and the transmembrane receptor Tie1 during the development of subpopulations of the zebrafish facial lymphatic network. This specific aspect of the facial network for...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-04-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/82969 |
| _version_ | 1797839628302024704 |
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| author | Melina Hußmann Dörte Schulte Sarah Weischer Claudia Carlantoni Hiroyuki Nakajima Naoki Mochizuki Didier YR Stainier Thomas Zobel Manuel Koch Stefan Schulte-Merker |
| author_facet | Melina Hußmann Dörte Schulte Sarah Weischer Claudia Carlantoni Hiroyuki Nakajima Naoki Mochizuki Didier YR Stainier Thomas Zobel Manuel Koch Stefan Schulte-Merker |
| author_sort | Melina Hußmann |
| collection | DOAJ |
| description | Multiple factors are required to form functional lymphatic vessels. Here, we uncover an essential role for the secreted protein Svep1 and the transmembrane receptor Tie1 during the development of subpopulations of the zebrafish facial lymphatic network. This specific aspect of the facial network forms independently of Vascular endothelial growth factor C (Vegfc) signalling, which otherwise is the most prominent signalling axis in all other lymphatic beds. Additionally, we find that multiple specific and newly uncovered phenotypic hallmarks of svep1 mutants are also present in tie1, but not in tie2 or vegfc mutants. These phenotypes are observed in the lymphatic vasculature of both head and trunk, as well as in the development of the dorsal longitudinal anastomotic vessel under reduced flow conditions. Therefore, our study demonstrates an important function for Tie1 signalling during lymphangiogenesis as well as blood vessel development in zebrafish. Furthermore, we show genetic interaction between svep1 and tie1 in vivo, during early steps of lymphangiogenesis, and demonstrate that zebrafish as well as human Svep1/SVEP1 protein bind to the respective Tie1/TIE1 receptors in vitro. Since compound heterozygous mutations for SVEP1 and TIE2 have recently been reported in human glaucoma patients, our data have clinical relevance in demonstrating a role for SVEP1 in TIE signalling in an in vivo setting. |
| first_indexed | 2024-04-09T16:01:06Z |
| format | Article |
| id | doaj.art-c2f4f50741844efe8ad2f64ab72baf45 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-09T16:01:06Z |
| publishDate | 2023-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c2f4f50741844efe8ad2f64ab72baf452023-04-25T12:14:08ZengeLife Sciences Publications LtdeLife2050-084X2023-04-011210.7554/eLife.82969Svep1 is a binding ligand of Tie1 and affects specific aspects of facial lymphatic development in a Vegfc-independent mannerMelina Hußmann0https://orcid.org/0000-0003-4798-7503Dörte Schulte1Sarah Weischer2https://orcid.org/0000-0001-7292-8308Claudia Carlantoni3https://orcid.org/0000-0003-3716-8539Hiroyuki Nakajima4Naoki Mochizuki5https://orcid.org/0000-0002-3938-9602Didier YR Stainier6https://orcid.org/0000-0002-0382-0026Thomas Zobel7Manuel Koch8Stefan Schulte-Merker9https://orcid.org/0000-0003-3617-8807Institute of Cardiovascular Organogenesis and Regeneration, Faculty of Medicine, WWU Münster, Münster, GermanyInstitute of Cardiovascular Organogenesis and Regeneration, Faculty of Medicine, WWU Münster, Münster, GermanyMünster Imaging Network, Cells in Motion Interfaculty Centre, Faculty of Biology, WWU Münster, Münster, GermanyMax Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim, GermanyDepartment of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Osaka, JapanDepartment of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Osaka, JapanMax Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim, GermanyMünster Imaging Network, Cells in Motion Interfaculty Centre, WWU Münster, Münster, GermanyInstitute for Dental Research and Oral Musculoskeletal Biology, Center for Biochemistry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyInstitute of Cardiovascular Organogenesis and Regeneration, Faculty of Medicine, WWU Münster, Münster, GermanyMultiple factors are required to form functional lymphatic vessels. Here, we uncover an essential role for the secreted protein Svep1 and the transmembrane receptor Tie1 during the development of subpopulations of the zebrafish facial lymphatic network. This specific aspect of the facial network forms independently of Vascular endothelial growth factor C (Vegfc) signalling, which otherwise is the most prominent signalling axis in all other lymphatic beds. Additionally, we find that multiple specific and newly uncovered phenotypic hallmarks of svep1 mutants are also present in tie1, but not in tie2 or vegfc mutants. These phenotypes are observed in the lymphatic vasculature of both head and trunk, as well as in the development of the dorsal longitudinal anastomotic vessel under reduced flow conditions. Therefore, our study demonstrates an important function for Tie1 signalling during lymphangiogenesis as well as blood vessel development in zebrafish. Furthermore, we show genetic interaction between svep1 and tie1 in vivo, during early steps of lymphangiogenesis, and demonstrate that zebrafish as well as human Svep1/SVEP1 protein bind to the respective Tie1/TIE1 receptors in vitro. Since compound heterozygous mutations for SVEP1 and TIE2 have recently been reported in human glaucoma patients, our data have clinical relevance in demonstrating a role for SVEP1 in TIE signalling in an in vivo setting.https://elifesciences.org/articles/82969lymphangiogenesisendothelial cellscell migration |
| spellingShingle | Melina Hußmann Dörte Schulte Sarah Weischer Claudia Carlantoni Hiroyuki Nakajima Naoki Mochizuki Didier YR Stainier Thomas Zobel Manuel Koch Stefan Schulte-Merker Svep1 is a binding ligand of Tie1 and affects specific aspects of facial lymphatic development in a Vegfc-independent manner eLife lymphangiogenesis endothelial cells cell migration |
| title | Svep1 is a binding ligand of Tie1 and affects specific aspects of facial lymphatic development in a Vegfc-independent manner |
| title_full | Svep1 is a binding ligand of Tie1 and affects specific aspects of facial lymphatic development in a Vegfc-independent manner |
| title_fullStr | Svep1 is a binding ligand of Tie1 and affects specific aspects of facial lymphatic development in a Vegfc-independent manner |
| title_full_unstemmed | Svep1 is a binding ligand of Tie1 and affects specific aspects of facial lymphatic development in a Vegfc-independent manner |
| title_short | Svep1 is a binding ligand of Tie1 and affects specific aspects of facial lymphatic development in a Vegfc-independent manner |
| title_sort | svep1 is a binding ligand of tie1 and affects specific aspects of facial lymphatic development in a vegfc independent manner |
| topic | lymphangiogenesis endothelial cells cell migration |
| url | https://elifesciences.org/articles/82969 |
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