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P130Cas/bcar1 mediates zebrafish caudal vein plexus angiogenesis

P130CAS/BCAR1 belongs to the CAS family of adaptor proteins, with important regulatory roles in cell migration, cell cycle control, and apoptosis. Previously, we and others showed that P130CAS mediates VEGF-A and PDGF signalling in vitro, but its cardiovascular function in vivo remains relatively un...

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Autores principales: Wisniewski, Laura, French, Vanessa, Lockwood, Nicola, Valdivia, Leonardo E., Frankel, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518251/
https://www.ncbi.nlm.nih.gov/pubmed/32973180
http://dx.doi.org/10.1038/s41598-020-71753-w
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author Wisniewski, Laura
French, Vanessa
Lockwood, Nicola
Valdivia, Leonardo E.
Frankel, Paul
author_facet Wisniewski, Laura
French, Vanessa
Lockwood, Nicola
Valdivia, Leonardo E.
Frankel, Paul
author_sort Wisniewski, Laura
collection PubMed
description P130CAS/BCAR1 belongs to the CAS family of adaptor proteins, with important regulatory roles in cell migration, cell cycle control, and apoptosis. Previously, we and others showed that P130CAS mediates VEGF-A and PDGF signalling in vitro, but its cardiovascular function in vivo remains relatively unexplored. We characterise here a novel deletion model of P130CAS in zebrafish. Using in vivo microscopy and transgenic vascular reporters, we observed that while bcar1−/− zebrafish showed no arterial angiogenic or heart defects during development, they strikingly failed to form the caudal vein plexus (CVP). Endothelial cells (ECs) within the CVP of bcar1−/− embryos produced fewer filopodial structures and did not detach efficiently from neighbouring cells, resulting in a significant reduction in ventral extension and overall CVP area. Mechanistically, we show that P130Cas mediates Bmp2b-induced ectopic angiogenic sprouting of ECs in the developing embryo and provide pharmacological evidence for a role of Src family kinases in CVP development.
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spelling pubmed-75182512020-09-29 P130Cas/bcar1 mediates zebrafish caudal vein plexus angiogenesis Wisniewski, Laura French, Vanessa Lockwood, Nicola Valdivia, Leonardo E. Frankel, Paul Sci Rep Article P130CAS/BCAR1 belongs to the CAS family of adaptor proteins, with important regulatory roles in cell migration, cell cycle control, and apoptosis. Previously, we and others showed that P130CAS mediates VEGF-A and PDGF signalling in vitro, but its cardiovascular function in vivo remains relatively unexplored. We characterise here a novel deletion model of P130CAS in zebrafish. Using in vivo microscopy and transgenic vascular reporters, we observed that while bcar1−/− zebrafish showed no arterial angiogenic or heart defects during development, they strikingly failed to form the caudal vein plexus (CVP). Endothelial cells (ECs) within the CVP of bcar1−/− embryos produced fewer filopodial structures and did not detach efficiently from neighbouring cells, resulting in a significant reduction in ventral extension and overall CVP area. Mechanistically, we show that P130Cas mediates Bmp2b-induced ectopic angiogenic sprouting of ECs in the developing embryo and provide pharmacological evidence for a role of Src family kinases in CVP development. Nature Publishing Group UK 2020-09-24 /pmc/articles/PMC7518251/ /pubmed/32973180 http://dx.doi.org/10.1038/s41598-020-71753-w Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wisniewski, Laura
French, Vanessa
Lockwood, Nicola
Valdivia, Leonardo E.
Frankel, Paul
P130Cas/bcar1 mediates zebrafish caudal vein plexus angiogenesis
title P130Cas/bcar1 mediates zebrafish caudal vein plexus angiogenesis
title_full P130Cas/bcar1 mediates zebrafish caudal vein plexus angiogenesis
title_fullStr P130Cas/bcar1 mediates zebrafish caudal vein plexus angiogenesis
title_full_unstemmed P130Cas/bcar1 mediates zebrafish caudal vein plexus angiogenesis
title_short P130Cas/bcar1 mediates zebrafish caudal vein plexus angiogenesis
title_sort p130cas/bcar1 mediates zebrafish caudal vein plexus angiogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518251/
https://www.ncbi.nlm.nih.gov/pubmed/32973180
http://dx.doi.org/10.1038/s41598-020-71753-w
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