2026-04-29T07:21:36Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/89292024-09-27T08:44:22Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607
Repisalud
author
Travisano, Stanislao Igor
author
Oliveira, Vera Lucia
author
Prados, Belen
author
Grego-Bessa, Joaquim
author
Piñeiro-Sabarís, Rebeca
author
Bou, Vanesa
author
Gomez, Manuel J
author
Sanchez-Cabo, Fatima
author
MacGrogan, Donal
author
de la Pompa, Jose Luis
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Fundación BBVA
funder
Fundación La Marató TV3
funder
Comunidad de Madrid (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Fundación ProCNIC
2020-01-29T08:56:17Z
2020-01-29T08:56:17Z
2019-12
Elife. 2019; 8:e49977
2050-084X
http://hdl.handle.net/20.500.12105/8929
31789590
10.7554/eLife.49977
2050-084X
eLife
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.
eng
EphrinB2
NOTCH
Coronaries
Developmental biology
Erial-venous differentiation
Mouse
Sinus venosus
Vessel morphogenesis
Coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade
journal article
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URL
https://repisalud.isciii.es/bitstreams/4b803a10-5e37-4b38-8d29-2893685ad940/download
File
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application/pdf
CoronaryArterialDevelopmentRegulated_2019.pdf
URL
https://repisalud.isciii.es/bitstreams/7261d9cd-8243-4dca-adb4-10bd45cbd708/download
File
MD5
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text/plain
CoronaryArterialDevelopmentRegulated_2019.pdf.txt