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The Prox1–Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors
The mammalian lymphatic vasculature is important for returning fluids from the extracellular tissue milieu back to the blood circulation. We showed previously that Prox1 dosage is important for the development of the mammalian lymphatic vasculature. The lack of Prox1 activity results in the complete...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180978/ https://www.ncbi.nlm.nih.gov/pubmed/25274728 http://dx.doi.org/10.1101/gad.216226.113 |
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author | Srinivasan, R. Sathish Escobedo, Noelia Yang, Ying Interiano, Ashley Dillard, Miriam E. Finkelstein, David Mukatira, Suraj Gil, Hyea Jin Nurmi, Harri Alitalo, Kari Oliver, Guillermo |
author_facet | Srinivasan, R. Sathish Escobedo, Noelia Yang, Ying Interiano, Ashley Dillard, Miriam E. Finkelstein, David Mukatira, Suraj Gil, Hyea Jin Nurmi, Harri Alitalo, Kari Oliver, Guillermo |
author_sort | Srinivasan, R. Sathish |
collection | PubMed |
description | The mammalian lymphatic vasculature is important for returning fluids from the extracellular tissue milieu back to the blood circulation. We showed previously that Prox1 dosage is important for the development of the mammalian lymphatic vasculature. The lack of Prox1 activity results in the complete absence of lymphatic endothelial cells (LECs). In Prox1 heterozygous embryos, the number of LECs is reduced because of a decrease in the progenitor pool in the cardinal vein. This reduction is caused by some progenitor cells being unable to maintain Prox1 expression. In this study, we identified Vegfr3, the cognate receptor of the lymphangiogenic growth factor Vegfc, as a dosage-dependent, direct in vivo target of Prox1. Using various mouse models, we also determined that Vegfr3 regulates Prox1 by establishing a feedback loop necessary to maintain the identity of LEC progenitors and that Vegfc-mediated activation of Vegfr3 signaling is necessary to maintain Prox1 expression in LEC progenitors. We propose that this feedback loop is the main sensing mechanism controlling the number of LEC progenitors and, as a consequence, the number of budding LECs that will form the embryonic lymphatic vasculature. |
format | Online Article Text |
id | pubmed-4180978 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-41809782015-04-01 The Prox1–Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors Srinivasan, R. Sathish Escobedo, Noelia Yang, Ying Interiano, Ashley Dillard, Miriam E. Finkelstein, David Mukatira, Suraj Gil, Hyea Jin Nurmi, Harri Alitalo, Kari Oliver, Guillermo Genes Dev Research Paper The mammalian lymphatic vasculature is important for returning fluids from the extracellular tissue milieu back to the blood circulation. We showed previously that Prox1 dosage is important for the development of the mammalian lymphatic vasculature. The lack of Prox1 activity results in the complete absence of lymphatic endothelial cells (LECs). In Prox1 heterozygous embryos, the number of LECs is reduced because of a decrease in the progenitor pool in the cardinal vein. This reduction is caused by some progenitor cells being unable to maintain Prox1 expression. In this study, we identified Vegfr3, the cognate receptor of the lymphangiogenic growth factor Vegfc, as a dosage-dependent, direct in vivo target of Prox1. Using various mouse models, we also determined that Vegfr3 regulates Prox1 by establishing a feedback loop necessary to maintain the identity of LEC progenitors and that Vegfc-mediated activation of Vegfr3 signaling is necessary to maintain Prox1 expression in LEC progenitors. We propose that this feedback loop is the main sensing mechanism controlling the number of LEC progenitors and, as a consequence, the number of budding LECs that will form the embryonic lymphatic vasculature. Cold Spring Harbor Laboratory Press 2014-10-01 /pmc/articles/PMC4180978/ /pubmed/25274728 http://dx.doi.org/10.1101/gad.216226.113 Text en © 2014 Srinivasan et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Paper Srinivasan, R. Sathish Escobedo, Noelia Yang, Ying Interiano, Ashley Dillard, Miriam E. Finkelstein, David Mukatira, Suraj Gil, Hyea Jin Nurmi, Harri Alitalo, Kari Oliver, Guillermo The Prox1–Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors |
title | The Prox1–Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors |
title_full | The Prox1–Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors |
title_fullStr | The Prox1–Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors |
title_full_unstemmed | The Prox1–Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors |
title_short | The Prox1–Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors |
title_sort | prox1–vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180978/ https://www.ncbi.nlm.nih.gov/pubmed/25274728 http://dx.doi.org/10.1101/gad.216226.113 |
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