Endothelial Jagged1 Antagonizes Dll4/Notch Signaling in Decidual Angiogenesis during Early Mouse Pregnancy

Autor: Jan Kitajewski, Nataki C. Douglas, Aimee M. Beaulieu, Salma Begum, Nuriban Valero-Pacheco, Nicole M. Marchetto, Christina C. Yarborough, Tracy Wu, Carrie J. Shawber, Valerie O’Besso
Rok vydání: 2020
Předmět:
Angiogenesis
lcsh:Chemistry
angiogenesis
Endometrium
Mice
Pregnancy
Morphogenesis
capillaries
lcsh:QH301-705.5
Spectroscopy
Neovascularization
Pathologic
Receptors
Notch
Decidua
Intracellular Signaling Peptides and Proteins
General Medicine
Computer Science Applications
Cell biology
Endothelial stem cell
medicine.anatomical_structure
Female
Jag1
Signal Transduction
JAG1
Spiral artery
Notch
Notch signaling pathway
Embryonic Development
Neovascularization
Physiologic
Dll4
Biology
Article
spiral arteries
Catalysis
Inorganic Chemistry
medicine
Animals
Embryo Implantation
Physical and Theoretical Chemistry
HEY2
Molecular Biology
Cell Proliferation
Calcium-Binding Proteins
Organic Chemistry
Endothelial Cells
Membrane Proteins
Placentation
Vascular Endothelial Growth Factor Receptor-2
Mice
Inbred C57BL
lcsh:Biology (General)
lcsh:QD1-999
Jagged-1 Protein
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 21, Iss 6477, p 6477 (2020)
Volume 21
Issue 18
ISSN: 1422-0067
DOI: 10.3390/ijms21186477
Popis: Maternal spiral arteries and newly formed decidual capillaries support embryonic development prior to placentation. Previous studies demonstrated that Notch signaling is active in endothelial cells of both decidual capillaries and spiral arteries, however the role of Notch signaling in physiologic decidual angiogenesis and maintenance of the decidual vasculature in early mouse pregnancy has not yet been fully elucidated. We used the Cdh5-CreERT2
Jagged1(Jag1)flox/flox (Jag1∆EC) mouse model to delete Notch ligand, Jag1, in maternal endothelial cells during post-implantation, pre-placentation mouse pregnancy. Loss of endothelial Jag1 leads to increased expression of Notch effectors, Hey2 and Nrarp, and increased endothelial Notch signaling activity in areas of the decidua with remodeling angiogenesis. This correlated with an increase in Dll4 expression in capillary endothelial cells, but not spiral artery endothelial cells. Consistent with increased Dll4/Notch signaling, we observed decreased VEGFR2 expression and endothelial cell proliferation in angiogenic decidual capillaries. Despite aberrant Dll4 expression and Notch activation in Jag1∆EC mutants, pregnancies were maintained and the decidual vasculature was not altered up to embryonic day 7.5. Thus, Jag1 functions in the newly formed decidual capillaries as an antagonist of endothelial Dll4/Notch signaling during angiogenesis, but Jag1 signaling is not necessary for early uterine angiogenesis.
Databáze: OpenAIRE
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