Molecular identification of venous progenitors in the dorsal aorta reveals an aortic origin for the cardinal vein in mammals
| Autor: | Tyson N. Kim, Henrik Lindskog, Yupeng Kong, Salvador Guevara-Gallardo, Eric B. Jelin, Yung Hae Kim, Rong Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
biology
Angiogenesis Stem Cells Connexin Endothelial Cells Neovascularization Physiologic Mice Transgenic biology.organism_classification Receptor tyrosine kinase Cell biology Veins Dorsal aorta Mice Immunology biology.protein Animals Progenitor cell Signal transduction Molecular Biology Zebrafish COUP-TFII Research Articles Aorta Developmental Biology Signal Transduction |
| Popis: | Coordinated arterial-venous differentiation is crucial for vascular development and function. The origin of the cardinal vein (CV) in mammals is unknown, while conflicting theories have been reported in chick and zebrafish. Here, we provide the first molecular characterization of endothelial cells (ECs) expressing venous molecular markers, or venous-fated ECs, within the emergent dorsal aorta (DA). These ECs, expressing the venous molecular markers Coup-TFII and EphB4, cohabited the early DA with ECs expressing the arterial molecular markers ephrin B2, Notch and connexin 40. These mixed ECs in the early DA expressed either the arterial or venous molecular marker, but rarely both. Subsequently, the DA exhibited uniform arterial markers. Real-time imaging of mouse embryos revealed EC movement from the DA to the CV during the stage when venous-fated ECs occupied the DA. We analyzed mutants for EphB4, which encodes a receptor tyrosine kinase for the ephrin B2 ligand, as we hypothesized that ephrin B2/EphB4 signaling may mediate the repulsion of venous-fated ECs from the DA to the CV. Using an EC quantification approach, we discovered that venous-fated ECs increased in the DA and decreased in the CV in the mutants, whereas the rest of the ECs in each vessel were unaffected. This result suggests that the venous-fated ECs were retained in the DA and missing in the CV in the EphB4 mutant, and thus that ephrin B2/EphB4 signaling normally functions to clear venous-fated ECs from the DA to the CV by cell repulsion. Therefore, our cellular and molecular evidence suggests that the DA harbors venous progenitors that move to participate in CV formation, and that ephrin B2/EphB4 signaling regulates this aortic contribution to the mammalian CV. |
| Databáze: | OpenAIRE |
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