A blood capillary plexus-derived population of progenitor cells contributes to genesis of the dermal lymphatic vasculature during embryonic development

Cathy Pichol-Thievend, Kelly L. Betterman, Xiaolei Liu, Wanshu Ma, Renae Skoczylas, Emmanuelle Lesieur, Frank L. Bos, Dorte Schulte, Stefan Schulte-Merker, Benjamin M. Hogan, Guillermo Oliver, Natasha L. Harvey*, Mathias Francois

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Despite the essential role of the lymphatic vasculature in tissue homeostasis and disease, knowledge of the organ-specific origins of lymphatic endothelial progenitor cells remains limited. The assumption that most murine embryonic lymphatic endothelial cells (LECs) are venous derived has recently been challenged. Here, we show that the embryonic dermal blood capillary plexus constitutes an additional, local source of LECs that contributes to the formation of the dermal lymphatic vascular network. We describe a novel mechanism whereby rare PROX1-positive endothelial cells exit the capillary plexus in a Ccbe1-dependent manner to establish discrete LEC clusters. As development proceeds, these clusters expand and further contribute to the growing lymphatic system. Lineage tracing and analyses of Gata2-deficient mice confirmed that these clusters are endothelial in origin. Furthermore, ectopic expression of Vegfc in the vasculature increased the number of PROX1-positive progenitors within the capillary bed. Our work reveals a novel source of lymphatic endothelial progenitors employed during construction of the dermal lymphatic vasculature and demonstrates that the blood vasculature is likely to remain an ongoing source of LECs during organogenesis, raising the question of whether a similar mechanism operates during pathological lymphangiogenesis.

Original languageEnglish (US)
Article numberdev160184
JournalDevelopment (Cambridge)
Volume145
Issue number10
DOIs
StatePublished - May 2018

Keywords

  • Lineage tracing
  • Lymphangiogenesis
  • Lymphatic endothelial cells
  • Mouse genetics
  • PROX1
  • Progenitor cell
  • Skin

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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    Pichol-Thievend, C., Betterman, K. L., Liu, X., Ma, W., Skoczylas, R., Lesieur, E., Bos, F. L., Schulte, D., Schulte-Merker, S., Hogan, B. M., Oliver, G., Harvey, N. L., & Francois, M. (2018). A blood capillary plexus-derived population of progenitor cells contributes to genesis of the dermal lymphatic vasculature during embryonic development. Development (Cambridge), 145(10), [dev160184]. https://doi.org/10.1242/dev.160184