The cytoskeleton adaptor protein Sorbs1 controls the development of lymphatic and venous vessels in zebrafish
Abstract Background Lymphangiogenesis, the formation of lymphatic vessels, is tightly linked to the development of the venous vasculature, both at the cellular and molecular levels. Here, we identify a novel role for Sorbs1, the founding member of the SoHo family of cytoskeleton adaptor proteins, in...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | BMC Biology |
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| Online Access: | https://doi.org/10.1186/s12915-024-01850-z |
| _version_ | 1797273272734187520 |
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| author | Alexandra Veloso Anouk Bleuart Louise Conrard Tanguy Orban Jonathan Bruyr Pauline Cabochette Raoul F. V. Germano Giel Schevenels Alice Bernard Egor Zindy Sofie Demeyer Benoit Vanhollebeke Franck Dequiedt Maud Martin |
| author_facet | Alexandra Veloso Anouk Bleuart Louise Conrard Tanguy Orban Jonathan Bruyr Pauline Cabochette Raoul F. V. Germano Giel Schevenels Alice Bernard Egor Zindy Sofie Demeyer Benoit Vanhollebeke Franck Dequiedt Maud Martin |
| author_sort | Alexandra Veloso |
| collection | DOAJ |
| description | Abstract Background Lymphangiogenesis, the formation of lymphatic vessels, is tightly linked to the development of the venous vasculature, both at the cellular and molecular levels. Here, we identify a novel role for Sorbs1, the founding member of the SoHo family of cytoskeleton adaptor proteins, in vascular and lymphatic development in the zebrafish. Results We show that Sorbs1 is required for secondary sprouting and emergence of several vascular structures specifically derived from the axial vein. Most notably, formation of the precursor parachordal lymphatic structures is affected in sorbs1 mutant embryos, severely impacting the establishment of the trunk lymphatic vessel network. Interestingly, we show that Sorbs1 interacts with the BMP pathway and could function outside of Vegfc signaling. Mechanistically, Sorbs1 controls FAK/Src signaling and subsequently impacts on the cytoskeleton processes regulated by Rac1 and RhoA GTPases. Inactivation of Sorbs1 altered cell-extracellular matrix (ECM) contacts rearrangement and cytoskeleton dynamics, leading to specific defects in endothelial cell migratory and adhesive properties. Conclusions Overall, using in vitro and in vivo assays, we identify Sorbs1 as an important regulator of venous and lymphatic angiogenesis independently of the Vegfc signaling axis. These results provide a better understanding of the complexity found within context-specific vascular and lymphatic development. |
| first_indexed | 2024-03-07T14:41:08Z |
| format | Article |
| id | doaj.art-c363338c59c147acad9ab5d4c4848971 |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-03-07T14:41:08Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-c363338c59c147acad9ab5d4c48489712024-03-05T20:21:53ZengBMCBMC Biology1741-70072024-02-0122112310.1186/s12915-024-01850-zThe cytoskeleton adaptor protein Sorbs1 controls the development of lymphatic and venous vessels in zebrafishAlexandra Veloso0Anouk Bleuart1Louise Conrard2Tanguy Orban3Jonathan Bruyr4Pauline Cabochette5Raoul F. V. Germano6Giel Schevenels7Alice Bernard8Egor Zindy9Sofie Demeyer10Benoit Vanhollebeke11Franck Dequiedt12Maud Martin13Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULiège)Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULiège)Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles (ULB)Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULiège)Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULiège)Department of Molecular Biology, Laboratory of Neurovascular Signaling, ULB Neuroscience Institute, Université Libre de Bruxelles (ULB)Department of Molecular Biology, Laboratory of Neurovascular Signaling, ULB Neuroscience Institute, Université Libre de Bruxelles (ULB)Department of Molecular Biology, Laboratory of Neurovascular Signaling, ULB Neuroscience Institute, Université Libre de Bruxelles (ULB)Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULiège)Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles (ULB)Laboratory for the Molecular Biology of Leukemia, Center for Human Genetics, KU LeuvenDepartment of Molecular Biology, Laboratory of Neurovascular Signaling, ULB Neuroscience Institute, Université Libre de Bruxelles (ULB)Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULiège)Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULiège)Abstract Background Lymphangiogenesis, the formation of lymphatic vessels, is tightly linked to the development of the venous vasculature, both at the cellular and molecular levels. Here, we identify a novel role for Sorbs1, the founding member of the SoHo family of cytoskeleton adaptor proteins, in vascular and lymphatic development in the zebrafish. Results We show that Sorbs1 is required for secondary sprouting and emergence of several vascular structures specifically derived from the axial vein. Most notably, formation of the precursor parachordal lymphatic structures is affected in sorbs1 mutant embryos, severely impacting the establishment of the trunk lymphatic vessel network. Interestingly, we show that Sorbs1 interacts with the BMP pathway and could function outside of Vegfc signaling. Mechanistically, Sorbs1 controls FAK/Src signaling and subsequently impacts on the cytoskeleton processes regulated by Rac1 and RhoA GTPases. Inactivation of Sorbs1 altered cell-extracellular matrix (ECM) contacts rearrangement and cytoskeleton dynamics, leading to specific defects in endothelial cell migratory and adhesive properties. Conclusions Overall, using in vitro and in vivo assays, we identify Sorbs1 as an important regulator of venous and lymphatic angiogenesis independently of the Vegfc signaling axis. These results provide a better understanding of the complexity found within context-specific vascular and lymphatic development.https://doi.org/10.1186/s12915-024-01850-zSorbs1LymphangiogenesisBMP signalingVegfcAngiogenesisRho GTPases |
| spellingShingle | Alexandra Veloso Anouk Bleuart Louise Conrard Tanguy Orban Jonathan Bruyr Pauline Cabochette Raoul F. V. Germano Giel Schevenels Alice Bernard Egor Zindy Sofie Demeyer Benoit Vanhollebeke Franck Dequiedt Maud Martin The cytoskeleton adaptor protein Sorbs1 controls the development of lymphatic and venous vessels in zebrafish BMC Biology Sorbs1 Lymphangiogenesis BMP signaling Vegfc Angiogenesis Rho GTPases |
| title | The cytoskeleton adaptor protein Sorbs1 controls the development of lymphatic and venous vessels in zebrafish |
| title_full | The cytoskeleton adaptor protein Sorbs1 controls the development of lymphatic and venous vessels in zebrafish |
| title_fullStr | The cytoskeleton adaptor protein Sorbs1 controls the development of lymphatic and venous vessels in zebrafish |
| title_full_unstemmed | The cytoskeleton adaptor protein Sorbs1 controls the development of lymphatic and venous vessels in zebrafish |
| title_short | The cytoskeleton adaptor protein Sorbs1 controls the development of lymphatic and venous vessels in zebrafish |
| title_sort | cytoskeleton adaptor protein sorbs1 controls the development of lymphatic and venous vessels in zebrafish |
| topic | Sorbs1 Lymphangiogenesis BMP signaling Vegfc Angiogenesis Rho GTPases |
| url | https://doi.org/10.1186/s12915-024-01850-z |
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