An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype
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The process of angiogenesis has been well documented, but little is known about the biology of lymphatic endothelial cells and the molecular mechanisms controlling lymphangiogenesis. The homeobox gene Prox1 is expressed in a subpopulation of endothelial cells that, after budding from veins, gives rise to the mammalian lymphatic system. In Prox1(-)(/-) embryos, this budding becomes arrested at around embryonic day (E)11.5, resulting in embryos without lymphatic vasculature. Unlike the endothelial cells that bud off in E11.5 wild-type embryos, those of Prox1-null embryos did not co-express any lymphatic markers such as VEGFR-3, LYVE-1 or SLC. Instead, the mutant cells appeared to have a blood vascular phenotype, as determined by their expression of laminin and CD34. These results suggest that Prox1 activity is required for both maintenance of the budding of the venous endothelial cells and differentiation toward the lymphatic phenotype. On the basis of our findings, we propose that a blood vascular phenotype is the default fate of budding embryonic venous endothelial cells; upon expression of Prox1, these budding cells adopt a lymphatic vasculature phenotype.
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PROX1 can function as a master regulator of lymphatic endothelial cells.
“Notably, PROX1 can function as an activator to promote neurogenesis in the brain39,40, or as a master regulator of lymphatic endothelial cells41,42.”
From Active repression of cell fate plasticity by PROX1 safeguards hepatocyte identity and prevents liver tumorigenesis (2025) · cites this paper as [42]
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- Authors
- Wigle, J. T., Harvey, N., Detmar, M., Lagutina, I., Grosveld, G., Gunn, M. D., Jackson, D. G., & Oliver, G.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Harvard University (US)
- Duke University (US)
- John Radcliffe Hospital (GB)
- Corresponding author
- Oliver, Guillermo
- Venue
- The EMBO Journal
- Published
- 2002-04-01
- Volume
- 21
- Issue
- 7
- Pages
- 1505-1513
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC125938
- OpenAlex
- W2096608993
- Cited by
- 943
- References
- 1
- Citations by year
- 2026: 23 · 2025: 35 · 2024: 35 · 2023: 32 · 2022: 41 · 2021: 46 · 2020: 32 · 2019: 36 · 2018: 26 · 2017: 35 · 2016: 40 · 2015: 32 · 2014: 42 · 2013: 36 · 2012: 28
- FWCI
- 19.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Lebanese Syrian Associated Charities (CA 21765)
- Medical Research Council Canada
- National Institutes of Health (CA21765))
- Medical Research Council
- National Eye Institute (R01EY012162, EY 12162)
- National Cancer Institute (CA21765, P30CA021765)
- National Institute of General Medical Sciences (GM58462, R01GM058462)
- Topics
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
- Health Sciences › Medicine › Surgery › Vascular Malformations and Hemangiomas
- Keywords
- Prox1, lymphatic endothelial cells, lymphangiogenesis, endothelial differentiation, VEGFR-3, LYVE-1, SLC, homeobox genes
- MeSH terms
- Prospero-Related Homeobox 1 Protein, Animals, Cell Differentiation, Endothelium, Vascular, Glycoproteins, Humans, Lymphatic System, Mice, Inbred BALB C, Mice, Nude, Neovascularization, Pathologic, Phenotype, Tumor Cells, Cultured, Biomarkers, Receptors, Growth Factor, Mice, Knockout, Homeodomain Proteins, Hyaluronan Receptors, Chemokines, CC, Receptor Protein-Tyrosine Kinases, Tumor Suppressor Proteins, Membrane Transport Proteins, Vesicular Transport Proteins, Vascular Endothelial Growth Factor Receptor-3, Mice, Chemokine CCL21
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