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An Evolutionarily Conserved Role for Polydom/Svep1 During Lymphatic Vessel Formation

RATIONALE: Lymphatic vessel formation and function constitutes a physiologically and pathophysiologically important process, but its genetic control is not well understood. OBJECTIVE: Here, we identify the secreted Polydom/Svep1 protein as essential for the formation of the lymphatic vasculature. We...

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Autores principales: Karpanen, Terhi, Padberg, Yvonne, van de Pavert, Serge A., Dierkes, Cathrin, Morooka, Nanami, Peterson-Maduro, Josi, van de Hoek, Glenn, Adrian, Max, Mochizuki, Naoki, Sekiguchi, Kiyotoshi, Kiefer, Friedemann, Schulte, Dörte, Schulte-Merker, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389596/
https://www.ncbi.nlm.nih.gov/pubmed/28179432
http://dx.doi.org/10.1161/CIRCRESAHA.116.308813
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author Karpanen, Terhi
Padberg, Yvonne
van de Pavert, Serge A.
Dierkes, Cathrin
Morooka, Nanami
Peterson-Maduro, Josi
van de Hoek, Glenn
Adrian, Max
Mochizuki, Naoki
Sekiguchi, Kiyotoshi
Kiefer, Friedemann
Schulte, Dörte
Schulte-Merker, Stefan
author_facet Karpanen, Terhi
Padberg, Yvonne
van de Pavert, Serge A.
Dierkes, Cathrin
Morooka, Nanami
Peterson-Maduro, Josi
van de Hoek, Glenn
Adrian, Max
Mochizuki, Naoki
Sekiguchi, Kiyotoshi
Kiefer, Friedemann
Schulte, Dörte
Schulte-Merker, Stefan
author_sort Karpanen, Terhi
collection PubMed
description RATIONALE: Lymphatic vessel formation and function constitutes a physiologically and pathophysiologically important process, but its genetic control is not well understood. OBJECTIVE: Here, we identify the secreted Polydom/Svep1 protein as essential for the formation of the lymphatic vasculature. We analyzed mutants in mice and zebrafish to gain insight into the role of Polydom/Svep1 in the lymphangiogenic process. METHODS AND RESULTS: Phenotypic analysis of zebrafish polydom/svep1 mutants showed a decrease in venous and lymphovenous sprouting, which leads to an increased number of intersegmental arteries. A reduced number of primordial lymphatic cells populated the horizontal myoseptum region but failed to migrate dorsally or ventrally, resulting in severe reduction of the lymphatic trunk vasculature. Corresponding mutants in the mouse Polydom/Svep1 gene showed normal egression of Prox-1(+) cells from the cardinal vein at E10.5, but at E12.5, the tight association between the cardinal vein and lymphatic endothelial cells at the first lymphovenous contact site was abnormal. Furthermore, mesenteric lymphatic structures at E18.5 failed to undergo remodeling events in mutants and lacked lymphatic valves. In both fish and mouse embryos, the expression of the gene suggests a nonendothelial and noncell autonomous mechanism. CONCLUSIONS: Our data identify zebrafish and mouse Polydom/Svep1 as essential extracellular factors for lymphangiogenesis. Expression of the respective genes by mesenchymal cells in intimate proximity with venous and lymphatic endothelial cells is required for sprouting and migratory events in zebrafish and for remodeling events of the lymphatic intraluminal valves in mouse embryos.
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spelling pubmed-53895962017-04-28 An Evolutionarily Conserved Role for Polydom/Svep1 During Lymphatic Vessel Formation Karpanen, Terhi Padberg, Yvonne van de Pavert, Serge A. Dierkes, Cathrin Morooka, Nanami Peterson-Maduro, Josi van de Hoek, Glenn Adrian, Max Mochizuki, Naoki Sekiguchi, Kiyotoshi Kiefer, Friedemann Schulte, Dörte Schulte-Merker, Stefan Circ Res Cellular Biology RATIONALE: Lymphatic vessel formation and function constitutes a physiologically and pathophysiologically important process, but its genetic control is not well understood. OBJECTIVE: Here, we identify the secreted Polydom/Svep1 protein as essential for the formation of the lymphatic vasculature. We analyzed mutants in mice and zebrafish to gain insight into the role of Polydom/Svep1 in the lymphangiogenic process. METHODS AND RESULTS: Phenotypic analysis of zebrafish polydom/svep1 mutants showed a decrease in venous and lymphovenous sprouting, which leads to an increased number of intersegmental arteries. A reduced number of primordial lymphatic cells populated the horizontal myoseptum region but failed to migrate dorsally or ventrally, resulting in severe reduction of the lymphatic trunk vasculature. Corresponding mutants in the mouse Polydom/Svep1 gene showed normal egression of Prox-1(+) cells from the cardinal vein at E10.5, but at E12.5, the tight association between the cardinal vein and lymphatic endothelial cells at the first lymphovenous contact site was abnormal. Furthermore, mesenteric lymphatic structures at E18.5 failed to undergo remodeling events in mutants and lacked lymphatic valves. In both fish and mouse embryos, the expression of the gene suggests a nonendothelial and noncell autonomous mechanism. CONCLUSIONS: Our data identify zebrafish and mouse Polydom/Svep1 as essential extracellular factors for lymphangiogenesis. Expression of the respective genes by mesenchymal cells in intimate proximity with venous and lymphatic endothelial cells is required for sprouting and migratory events in zebrafish and for remodeling events of the lymphatic intraluminal valves in mouse embryos. Lippincott Williams & Wilkins 2017-04-14 2017-04-13 /pmc/articles/PMC5389596/ /pubmed/28179432 http://dx.doi.org/10.1161/CIRCRESAHA.116.308813 Text en © 2017 The Authors. Circulation Research is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited and is not used for commercial purposes.
spellingShingle Cellular Biology
Karpanen, Terhi
Padberg, Yvonne
van de Pavert, Serge A.
Dierkes, Cathrin
Morooka, Nanami
Peterson-Maduro, Josi
van de Hoek, Glenn
Adrian, Max
Mochizuki, Naoki
Sekiguchi, Kiyotoshi
Kiefer, Friedemann
Schulte, Dörte
Schulte-Merker, Stefan
An Evolutionarily Conserved Role for Polydom/Svep1 During Lymphatic Vessel Formation
title An Evolutionarily Conserved Role for Polydom/Svep1 During Lymphatic Vessel Formation
title_full An Evolutionarily Conserved Role for Polydom/Svep1 During Lymphatic Vessel Formation
title_fullStr An Evolutionarily Conserved Role for Polydom/Svep1 During Lymphatic Vessel Formation
title_full_unstemmed An Evolutionarily Conserved Role for Polydom/Svep1 During Lymphatic Vessel Formation
title_short An Evolutionarily Conserved Role for Polydom/Svep1 During Lymphatic Vessel Formation
title_sort evolutionarily conserved role for polydom/svep1 during lymphatic vessel formation
topic Cellular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389596/
https://www.ncbi.nlm.nih.gov/pubmed/28179432
http://dx.doi.org/10.1161/CIRCRESAHA.116.308813
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