Coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade

Autor: Manuel Gómez, Vanesa Bou, Joaquim Grego-Bessa, José Luis de la Pompa, Donal MacGrogan, Rebeca Piñeiro-Sabarís, Vera Lucia Oliveira, Fátima Sánchez-Cabo, Belén Prados, Stanislao Igor Travisano
Přispěvatelé: Ministerio de Ciencia, Innovación y Universidades (España), Fundación BBVA, Fundacio la Marato, Comunidad de Madrid, European Regional Development Fund (ERDF/FEDER), Fundación ProCNIC
Rok vydání: 2019
Předmět:
0301 basic medicine
Mouse
Angiogenesis
Receptor expression
Ligands
vessel morphogenesis
Mice
0302 clinical medicine
Morphogenesis
Biology (General)
Hypoxia
Receptors
Notch
Chemistry
sinus venosus
General Neuroscience
Intracellular Signaling Peptides and Proteins
General Medicine
Coronary Vessels
Cell biology
NOTCH
medicine.anatomical_structure
erial-venous differentiation
cardiovascular system
Medicine
Signal Transduction
Research Article
EphrinB2
JAG1
QH301-705.5
Science
Heart Ventricles
Neovascularization
Physiologic
Ephrin-B2
Vascular Remodeling
General Biochemistry
Genetics and Molecular Biology
developmental biology
03 medical and health sciences
Stress
Physiological
Human Umbilical Vein Endothelial Cells
medicine
Animals
Humans
mouse
Endocardium
Sinus venosus
Plexus
NFATC Transcription Factors
coronaries
General Immunology and Microbiology
Membrane Proteins
Embryonic stem cell
030104 developmental biology
Mutation
Endothelium
Vascular
Transcriptome
Developmental biology
Jagged-1 Protein
030217 neurology & neurosurgery
Developmental Biology
Zdroj: eLife
Repisalud
Instituto de Salud Carlos III (ISCIII)
eLife, Vol 8 (2019)
ISSN: 2050-084X
Popis: 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. This study was supported by grants SAF2016-78370-R, CB16/11/00399 (CIBER CV), and RD16/0011/0021 (TERCEL) from the Spanish Ministry of Science, Innovation and Universities (MCIU) and grants from the Fundacion BBVA (Ref.: BIO14_298) and Fundacion La Marato (Ref.: 20153431) to JLDLP. JG-B is funded by Atraccion de Talento Program from the Comunidad de Madrid. The cost of this publication was supported in part with funds from the ERDF. The CNIC is supported by the MCIU and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015–0505). Sí
Databáze: OpenAIRE
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