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Coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade
Coronaries are essential for myocardial growth and heart function. Notch is crucial for mouse embryonic angiogenesis, but its role in coronary development remains uncertain. We show Jag1, Dll4 and activated Notch1 receptor expression in sinus venosus (SV) endocardium. Endocardial Jag1 removal blocks...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917494/ https://www.ncbi.nlm.nih.gov/pubmed/31789590 http://dx.doi.org/10.7554/eLife.49977 |
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author | Travisano, Stanislao Igor Oliveira, Vera Lucia Prados, Belén Grego-Bessa, Joaquim Piñeiro-Sabarís, Rebeca Bou, Vanesa Gómez, Manuel J Sánchez-Cabo, Fátima MacGrogan, Donal de la Pompa, José Luis |
author_facet | Travisano, Stanislao Igor Oliveira, Vera Lucia Prados, Belén Grego-Bessa, Joaquim Piñeiro-Sabarís, Rebeca Bou, Vanesa Gómez, Manuel J Sánchez-Cabo, Fátima MacGrogan, Donal de la Pompa, José Luis |
author_sort | Travisano, Stanislao Igor |
collection | PubMed |
description | Coronaries are essential for myocardial growth and heart function. Notch is crucial for mouse embryonic angiogenesis, but its role in coronary development remains uncertain. We show Jag1, Dll4 and activated Notch1 receptor expression in sinus venosus (SV) endocardium. Endocardial Jag1 removal blocks SV capillary sprouting, while Dll4 inactivation stimulates excessive capillary growth, suggesting that ligand antagonism regulates coronary primary plexus formation. Later endothelial ligand removal, or forced expression of Dll4 or the glycosyltransferase Mfng, blocks coronary plexus remodeling, arterial differentiation, and perivascular cell maturation. Endocardial deletion of Efnb2 phenocopies the coronary arterial defects of Notch mutants. Angiogenic rescue experiments in ventricular explants, or in primary human endothelial cells, indicate that EphrinB2 is a critical effector of antagonistic Dll4 and Jag1 functions in arterial morphogenesis. Thus, coronary arterial precursors are specified in the SV prior to primary coronary plexus formation and subsequent arterial differentiation depends on a Dll4-Jag1-EphrinB2 signaling cascade. |
format | Online Article Text |
id | pubmed-6917494 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-69174942019-12-18 Coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade Travisano, Stanislao Igor Oliveira, Vera Lucia Prados, Belén Grego-Bessa, Joaquim Piñeiro-Sabarís, Rebeca Bou, Vanesa Gómez, Manuel J Sánchez-Cabo, Fátima MacGrogan, Donal de la Pompa, José Luis eLife Developmental Biology Coronaries are essential for myocardial growth and heart function. Notch is crucial for mouse embryonic angiogenesis, but its role in coronary development remains uncertain. We show Jag1, Dll4 and activated Notch1 receptor expression in sinus venosus (SV) endocardium. Endocardial Jag1 removal blocks SV capillary sprouting, while Dll4 inactivation stimulates excessive capillary growth, suggesting that ligand antagonism regulates coronary primary plexus formation. Later endothelial ligand removal, or forced expression of Dll4 or the glycosyltransferase Mfng, blocks coronary plexus remodeling, arterial differentiation, and perivascular cell maturation. Endocardial deletion of Efnb2 phenocopies the coronary arterial defects of Notch mutants. Angiogenic rescue experiments in ventricular explants, or in primary human endothelial cells, indicate that EphrinB2 is a critical effector of antagonistic Dll4 and Jag1 functions in arterial morphogenesis. Thus, coronary arterial precursors are specified in the SV prior to primary coronary plexus formation and subsequent arterial differentiation depends on a Dll4-Jag1-EphrinB2 signaling cascade. eLife Sciences Publications, Ltd 2019-12-04 /pmc/articles/PMC6917494/ /pubmed/31789590 http://dx.doi.org/10.7554/eLife.49977 Text en © 2019, Travisano et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Developmental Biology Travisano, Stanislao Igor Oliveira, Vera Lucia Prados, Belén Grego-Bessa, Joaquim Piñeiro-Sabarís, Rebeca Bou, Vanesa Gómez, Manuel J Sánchez-Cabo, Fátima MacGrogan, Donal de la Pompa, José Luis Coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade |
title | Coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade |
title_full | Coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade |
title_fullStr | Coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade |
title_full_unstemmed | Coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade |
title_short | Coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade |
title_sort | coronary arterial development is regulated by a dll4-jag1-ephrinb2 signaling cascade |
topic | Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917494/ https://www.ncbi.nlm.nih.gov/pubmed/31789590 http://dx.doi.org/10.7554/eLife.49977 |
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