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ResearchIn-Press PreviewDevelopmentReproductive biologyVascular biology Open Access | 10.1172/jci.insight.194461

Dll4 assembles the umbilical cord and placental vasculature

Derek C. Sung,1 Hana A. Ahanger,1 Sweta Narayan,1 Jesse A. Pace,1 Mei Chen,1 Jisheng Yang,1 Siqi Gao,1 T.C.S. Keller IV,1 Jenna Bockman,1 Xiaowen Chen,1 Erica Nguyen,1 Alan T. Tang,1 Patricia Mericko-Ishizuka,1 Ivan Maillard,2 and Mark L. Kahn1

1Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, United States of America

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1Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, United States of America

Find articles by Ahanger, H. in: PubMed | Google Scholar

1Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, United States of America

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1Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, United States of America

Find articles by Pace, J. in: PubMed | Google Scholar

1Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, United States of America

Find articles by Chen, M. in: PubMed | Google Scholar

1Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, United States of America

Find articles by Yang, J. in: PubMed | Google Scholar

1Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, United States of America

Find articles by Gao, S. in: PubMed | Google Scholar

1Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, United States of America

Find articles by Keller IV, T. in: PubMed | Google Scholar |

1Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, United States of America

Find articles by Bockman, J. in: PubMed | Google Scholar

1Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, United States of America

Find articles by Chen, X. in: PubMed | Google Scholar

1Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, United States of America

Find articles by Nguyen, E. in: PubMed | Google Scholar

1Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, United States of America

Find articles by Tang, A. in: PubMed | Google Scholar |

1Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, United States of America

Find articles by Mericko-Ishizuka, P. in: PubMed | Google Scholar

1Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, United States of America

Find articles by Maillard, I. in: PubMed | Google Scholar |

1Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, United States of America

Find articles by Kahn, M. in: PubMed | Google Scholar |

Published February 17, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.194461.
Copyright © 2026, Sung et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published February 17, 2026 - Version history
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Abstract

Proper development of the umbilical cord and placental vasculature is essential for embryonic development. While the allantois is known give rise to endothelial cells (ECs) within the placenta, whether the allantois gives rise to ECs in the umbilical cord is debated. Furthermore, a lack of genetic tools to study placental vascular development independent of the embryo proper has hindered robust investigation into the primary cause of vascular defects from early studies utilizing global knockouts. In this study, we delineate the contribution of the allantois to the umbilical vessels and utilize a mouse genetic tool previously developed by our lab to revisit the role of Notch signaling during placental development. We show that the allantois has mosaic contribution to the umbilical endothelium with higher contributions closer to the placenta. Allantoic deletion of Dll4 disrupts umbilical cord and placental vascular formation with secondary defects in the heart. Lastly, we identify Unc5b downstream of Notch signaling that restricts EC migration while promoting chemokine signaling for smooth muscle cell (SMC) recruitment to arteries. These findings identify a genetic tool for investigating placental vascular development and give new insights into the ontogeny and mechanisms of placental vascular and umbilical cord development.

Version history
  • Version 1 (February 17, 2026): In-Press Preview
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