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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
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.
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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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