Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Lung inflammatory injury and tissue repair (Jul 2023)
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Development of the mammalian lymphatic vasculature
Ying Yang, Guillermo Oliver
Ying Yang, Guillermo Oliver
Published March 3, 2014
Citation Information: J Clin Invest. 2014;124(3):888-897. https://doi.org/10.1172/JCI71609.
View: Text | PDF
Review Series

Development of the mammalian lymphatic vasculature

  • Text
  • PDF
Abstract

The two vascular systems of our body are the blood and lymphatic vasculature. Our understanding of the cellular and molecular processes controlling the development of the lymphatic vasculature has progressed significantly in the last decade. In mammals, this is a stepwise process that starts in the embryonic veins, where lymphatic EC (LEC) progenitors are initially specified. The differentiation and maturation of these progenitors continues as they bud from the veins to produce scattered primitive lymph sacs, from which most of the lymphatic vasculature is derived. Here, we summarize our current understanding of the key steps leading to the formation of a functional lymphatic vasculature.

Authors

Ying Yang, Guillermo Oliver

×

Figure 1

Schematic representation of the development of the mammalian lymphatic vasculature.

Options: View larger image (or click on image) Download as PowerPoint
Schematic representation of the development of the mammalian lymphatic v...
(A) Sagittal view of the key temporal events that take place along the CV from E9.0 to E11.5 in the mouse embryo. The CV is the main source of LECs. Initially, among others, blood ECs in the CV and ISVs express the transcription factors COUP-TFII and SOX18. A few hours later (E9.5), the activity of SOX18 and COUP-TFII induces PROX1 expression in a subpopulation of venous ECs. The initiation of PROX1 expression indicates that LEC specification has started, and venous PROX1-expressing ECs are considered LEC progenitors. At around E10.5, most of those progenitors start to bud from the CV and ISVs. This process requires the graded expression of VEGF-C in the surrounding mesenchyme. Mediated by PROX1, budding LECs maintain the expression of VEGFR-3 and begin expressing PDPN once outside of the CV. The combined expression of these genes indicates that lymphatic differentiation is progressing. As LECs bud off in an interconnected manner, they assemble together, and at approximately E11.5 they start to form different lymph sacs. Following LEC proliferation and sprouting, the majority of the lymphatic network arises from these sacs. (B) Transverse representation of the LEC budding process. At around E10.5, PROX1+/PDPN+/VEGFR-3+-differentiating LECs bud from the CV and ISVs. The budding LECs migrate as an interconnected group of cells dorsally and longitudinally into the surrounding mesenchyme in the anterior region of the embryo.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts