Endothelial Jagged1 Antagonizes Dll4/Notch Signaling in Decidual Angiogenesis during Early Mouse Pregnancy
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 d...
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/18/6477 |
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| author | Nicole M. Marchetto Salma Begum Tracy Wu Valerie O’Besso Christina C. Yarborough Nuriban Valero-Pacheco Aimee M. Beaulieu Jan K. Kitajewski Carrie J. Shawber Nataki C. Douglas |
| author_facet | Nicole M. Marchetto Salma Begum Tracy Wu Valerie O’Besso Christina C. Yarborough Nuriban Valero-Pacheco Aimee M. Beaulieu Jan K. Kitajewski Carrie J. Shawber Nataki C. Douglas |
| author_sort | Nicole M. Marchetto |
| collection | DOAJ |
| description | 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 <i>Cdh5-Cre<sup>ERT2</sup>;</i><i>Jagged1(Jag1)<sup>flox/flox</sup></i> (<i>Jag1∆EC</i>) mouse model to delete Notch ligand, <i>Jag1</i>, in maternal endothelial cells during post-implantation, pre-placentation mouse pregnancy. Loss of endothelial <i>Jag1</i> leads to increased expression of Notch effectors, <i>Hey2</i> and <i>Nrarp,</i> 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 <i>Jag1∆EC</i> 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. |
| first_indexed | 2024-03-10T16:33:10Z |
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| language | English |
| last_indexed | 2024-03-10T16:33:10Z |
| publishDate | 2020-09-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b34b5e504f0647aea7020f2ce68263982023-11-20T12:40:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012118647710.3390/ijms21186477Endothelial Jagged1 Antagonizes Dll4/Notch Signaling in Decidual Angiogenesis during Early Mouse PregnancyNicole M. Marchetto0Salma Begum1Tracy Wu2Valerie O’Besso3Christina C. Yarborough4Nuriban Valero-Pacheco5Aimee M. Beaulieu6Jan K. Kitajewski7Carrie J. Shawber8Nataki C. Douglas9Department of Obstetrics, Gynecology and Reproductive Health, Rutgers New Jersey Medical School, Newark, NJ 07103, USADepartment of Obstetrics, Gynecology and Reproductive Health, Rutgers New Jersey Medical School, Newark, NJ 07103, USADepartment of Obstetrics, Gynecology and Reproductive Health, Rutgers New Jersey Medical School, Newark, NJ 07103, USARutgers New Jersey Medical School, Newark, NJ 07103, USASchool of Graduate Studies, Rutgers Biomedical and Health Sciences, Newark, NJ 07103, USADepartment of Microbiology, Biochemistry, and Molecular Genetics, Rutgers Biomedical and Health Sciences, Newark, NJ 07103, USADepartment of Microbiology, Biochemistry, and Molecular Genetics, Rutgers Biomedical and Health Sciences, Newark, NJ 07103, USADepartment of Physiology & Biophysics, University of Illinois Chicago, Chicago, IL 60612, USADepartment of Obstetrics and Gynecology, Division of Reproductive Sciences, Columbia University College of Physicians and Surgeons, New York, NY 10032, USADepartment of Obstetrics, Gynecology and Reproductive Health, Rutgers New Jersey Medical School, Newark, NJ 07103, USAMaternal 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 <i>Cdh5-Cre<sup>ERT2</sup>;</i><i>Jagged1(Jag1)<sup>flox/flox</sup></i> (<i>Jag1∆EC</i>) mouse model to delete Notch ligand, <i>Jag1</i>, in maternal endothelial cells during post-implantation, pre-placentation mouse pregnancy. Loss of endothelial <i>Jag1</i> leads to increased expression of Notch effectors, <i>Hey2</i> and <i>Nrarp,</i> 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 <i>Jag1∆EC</i> 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.https://www.mdpi.com/1422-0067/21/18/6477NotchJag1Dll4endothelial cellsdeciduaangiogenesis |
| spellingShingle | Nicole M. Marchetto Salma Begum Tracy Wu Valerie O’Besso Christina C. Yarborough Nuriban Valero-Pacheco Aimee M. Beaulieu Jan K. Kitajewski Carrie J. Shawber Nataki C. Douglas Endothelial Jagged1 Antagonizes Dll4/Notch Signaling in Decidual Angiogenesis during Early Mouse Pregnancy International Journal of Molecular Sciences Notch Jag1 Dll4 endothelial cells decidua angiogenesis |
| title | Endothelial Jagged1 Antagonizes Dll4/Notch Signaling in Decidual Angiogenesis during Early Mouse Pregnancy |
| title_full | Endothelial Jagged1 Antagonizes Dll4/Notch Signaling in Decidual Angiogenesis during Early Mouse Pregnancy |
| title_fullStr | Endothelial Jagged1 Antagonizes Dll4/Notch Signaling in Decidual Angiogenesis during Early Mouse Pregnancy |
| title_full_unstemmed | Endothelial Jagged1 Antagonizes Dll4/Notch Signaling in Decidual Angiogenesis during Early Mouse Pregnancy |
| title_short | Endothelial Jagged1 Antagonizes Dll4/Notch Signaling in Decidual Angiogenesis during Early Mouse Pregnancy |
| title_sort | endothelial jagged1 antagonizes dll4 notch signaling in decidual angiogenesis during early mouse pregnancy |
| topic | Notch Jag1 Dll4 endothelial cells decidua angiogenesis |
| url | https://www.mdpi.com/1422-0067/21/18/6477 |
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