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

International Journal of Molecular Sciences

AimeeM. Beaulieu¹  Nuriban Valero-Pacheco¹  CarrieJ. Shawber²  Salma Begum³  Tracy Wu³  NatakiC. Douglas³  NicoleM. Marchetto³  JanK. Kitajewski⁴  Valerie O’Besso⁵  ChristinaC. Yarborough⁶ 

[1] Department of Microbiology, Biochemistry, and Molecular Genetics, Rutgers Biomedical and Health Sciences, Newark, NJ 07103, USA;Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA;Department of Obstetrics, Gynecology and Reproductive Health, Rutgers New Jersey Medical School, Newark, NJ 07103, USA;Department of Physiology & Biophysics, University of Illinois Chicago, Chicago, IL 60612, USA;Rutgers New Jersey Medical School, Newark, NJ 07103, USA;School of Graduate Studies, Rutgers Biomedical and Health Sciences, Newark, NJ 07103, USA;

关键词: Notch;    Jag1;    Dll4;    endothelial cells;    decidua;    angiogenesis;   

DOI  :  10.3390/ijms21186477

来源: DOAJ

【 摘 要 】

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-Cre^ERT2;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.

【 授权许可】

Unknown