Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increased fibronectin, vcam 1 and integrin α4/β1
Aggregation of the Tar DNA-binding protein of 43 kDa (TDP-43) is a pathological hallmark of amyotrophic lateral sclerosis and frontotemporal dementia and likely contributes to disease by loss of nuclear function. Analysis of TDP-43 function in knockout zebrafish identified an endothelial directional...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1169962/full |
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| author | Katrin Hipke Katrin Hipke Bettina Pitter Alexander Hruscha Frauke van Bebber Miha Modic Miha Modic Miha Modic Vikas Bansal Sebastian A. Lewandowski Denise Orozco Dieter Edbauer Dieter Edbauer Dieter Edbauer Stefan Bonn Christian Haass Christian Haass Christian Haass Ulrich Pohl Ulrich Pohl Ulrich Pohl Ulrich Pohl Eloi Montanez Bettina Schmid Bettina Schmid |
| author_facet | Katrin Hipke Katrin Hipke Bettina Pitter Alexander Hruscha Frauke van Bebber Miha Modic Miha Modic Miha Modic Vikas Bansal Sebastian A. Lewandowski Denise Orozco Dieter Edbauer Dieter Edbauer Dieter Edbauer Stefan Bonn Christian Haass Christian Haass Christian Haass Ulrich Pohl Ulrich Pohl Ulrich Pohl Ulrich Pohl Eloi Montanez Bettina Schmid Bettina Schmid |
| author_sort | Katrin Hipke |
| collection | DOAJ |
| description | Aggregation of the Tar DNA-binding protein of 43 kDa (TDP-43) is a pathological hallmark of amyotrophic lateral sclerosis and frontotemporal dementia and likely contributes to disease by loss of nuclear function. Analysis of TDP-43 function in knockout zebrafish identified an endothelial directional migration and hypersprouting phenotype during development prior lethality. In human umbilical vein cells (HUVEC) the loss of TDP-43 leads to hyperbranching. We identified elevated expression of FIBRONECTIN 1 (FN1), the VASCULAR CELL ADHESION MOLECULE 1 (VCAM1), as well as their receptor INTEGRIN α4β1 (ITGA4B1) in HUVEC cells. Importantly, reducing the levels of ITGA4, FN1, and VCAM1 homologues in the TDP-43 loss-of-function zebrafish rescues the angiogenic defects indicating the conservation of human and zebrafish TDP-43 function during angiogenesis. Our study identifies a novel pathway regulated by TDP-43 important for angiogenesis during development. |
| first_indexed | 2024-03-13T05:57:46Z |
| format | Article |
| id | doaj.art-41783c87576d4c5381ad20b7824e8c6c |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-03-13T05:57:46Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-41783c87576d4c5381ad20b7824e8c6c2023-06-13T04:11:55ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-06-011110.3389/fcell.2023.11699621169962Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increased fibronectin, vcam 1 and integrin α4/β1Katrin Hipke0Katrin Hipke1Bettina Pitter2Alexander Hruscha3Frauke van Bebber4Miha Modic5Miha Modic6Miha Modic7Vikas Bansal8Sebastian A. Lewandowski9Denise Orozco10Dieter Edbauer11Dieter Edbauer12Dieter Edbauer13Stefan Bonn14Christian Haass15Christian Haass16Christian Haass17Ulrich Pohl18Ulrich Pohl19Ulrich Pohl20Ulrich Pohl21Eloi Montanez22Bettina Schmid23Bettina Schmid24German Center for Neurodegenerative Diseases (DZNE), Munich, GermanyMunich Cluster for Systems Neurology (SyNergy), Munich, GermanyWalter Brendel Center, Biomedical Center, Ludwig-Maximilians-University Munich, Munich, GermanyGerman Center for Neurodegenerative Diseases (DZNE), Munich, GermanyGerman Center for Neurodegenerative Diseases (DZNE), Munich, GermanyThe Francis Crick Institute, London, United KingdomDementia Research Institute at KCL, London, United KingdomNational Institute of Chemistry, Ljubljana, SloveniaGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, GermanyDepartment of Medical Biochemistry and Biophysics (MBB), Karolinska Institute, Stockholm, SwedenGerman Center for Neurodegenerative Diseases (DZNE), Munich, GermanyGerman Center for Neurodegenerative Diseases (DZNE), Munich, GermanyMunich Cluster for Systems Neurology (SyNergy), Munich, GermanyBiomedical Center, Ludwig-Maximilians-University Munich, Munich, Germany0Institute of Medical Systems Biology, Center for Biomedical AI (bAIome), Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyGerman Center for Neurodegenerative Diseases (DZNE), Munich, GermanyMunich Cluster for Systems Neurology (SyNergy), Munich, GermanyBiomedical Center, Ludwig-Maximilians-University Munich, Munich, GermanyMunich Cluster for Systems Neurology (SyNergy), Munich, GermanyWalter Brendel Center, Biomedical Center, Ludwig-Maximilians-University Munich, Munich, GermanyBiomedical Center, Ludwig-Maximilians-University Munich, Munich, Germany1DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany2Department of Physiological Sciences, Faculty of Medicine and Health Sciences, University of Barcelona and Bellvitge Biomedical Research Institute, Barcelona, SpainGerman Center for Neurodegenerative Diseases (DZNE), Munich, GermanyMunich Cluster for Systems Neurology (SyNergy), Munich, GermanyAggregation of the Tar DNA-binding protein of 43 kDa (TDP-43) is a pathological hallmark of amyotrophic lateral sclerosis and frontotemporal dementia and likely contributes to disease by loss of nuclear function. Analysis of TDP-43 function in knockout zebrafish identified an endothelial directional migration and hypersprouting phenotype during development prior lethality. In human umbilical vein cells (HUVEC) the loss of TDP-43 leads to hyperbranching. We identified elevated expression of FIBRONECTIN 1 (FN1), the VASCULAR CELL ADHESION MOLECULE 1 (VCAM1), as well as their receptor INTEGRIN α4β1 (ITGA4B1) in HUVEC cells. Importantly, reducing the levels of ITGA4, FN1, and VCAM1 homologues in the TDP-43 loss-of-function zebrafish rescues the angiogenic defects indicating the conservation of human and zebrafish TDP-43 function during angiogenesis. Our study identifies a novel pathway regulated by TDP-43 important for angiogenesis during development.https://www.frontiersin.org/articles/10.3389/fcell.2023.1169962/fullTDP-43angiogenesisneurodegenerationzebrafishALS |
| spellingShingle | Katrin Hipke Katrin Hipke Bettina Pitter Alexander Hruscha Frauke van Bebber Miha Modic Miha Modic Miha Modic Vikas Bansal Sebastian A. Lewandowski Denise Orozco Dieter Edbauer Dieter Edbauer Dieter Edbauer Stefan Bonn Christian Haass Christian Haass Christian Haass Ulrich Pohl Ulrich Pohl Ulrich Pohl Ulrich Pohl Eloi Montanez Bettina Schmid Bettina Schmid Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increased fibronectin, vcam 1 and integrin α4/β1 Frontiers in Cell and Developmental Biology TDP-43 angiogenesis neurodegeneration zebrafish ALS |
| title | Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increased fibronectin, vcam 1 and integrin α4/β1 |
| title_full | Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increased fibronectin, vcam 1 and integrin α4/β1 |
| title_fullStr | Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increased fibronectin, vcam 1 and integrin α4/β1 |
| title_full_unstemmed | Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increased fibronectin, vcam 1 and integrin α4/β1 |
| title_short | Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increased fibronectin, vcam 1 and integrin α4/β1 |
| title_sort | loss of tdp 43 causes ectopic endothelial sprouting and migration defects through increased fibronectin vcam 1 and integrin α4 β1 |
| topic | TDP-43 angiogenesis neurodegeneration zebrafish ALS |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1169962/full |
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