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A novel multistep mechanism for initial lymphangiogenesis in mouse embryos based on ultramicroscopy.
| Content Provider | Europe PMC |
|---|---|
| Author | Hägerling, René Pollmann, Cathrin Andreas, Martin Schmidt, Christian Nurmi, Harri Adams, Ralf H Alitalo, Kari Andresen, Volker Schulte-Merker, Stefan Kiefer, Friedemann |
| Copyright Year | 2013 |
| Abstract | During mammalian development, a subpopulation of endothelial cells in the cardinal vein (CV) expresses lymphatic-specific genes and subsequently develops into the first lymphatic structures, collectively termed as lymph sacs. Budding, sprouting and ballooning of lymphatic endothelial cells (LECs) have been proposed to underlie the emergence of LECs from the CV, but the exact mechanisms of lymph vessel formation remain poorly understood. Applying selective plane illumination-based ultramicroscopy to entire wholemount-immunostained mouse embryos, we visualized the complete developing vascular system with cellular resolution. Here, we report emergence of the earliest detectable LECs as strings of loosely connected cells between the CV and superficial venous plexus. Subsequent aggregation of LECs resulted in formation of two distinct, previously unidentified lymphatic structures, the dorsal peripheral longitudinal lymphatic vessel (PLLV) and the ventral primordial thoracic duct (pTD), which at later stages formed a direct contact with the CV. Providing new insights into their function, we found vascular endothelial growth factor C (VEGF-C) and the matrix component CCBE1 indispensable for LEC budding and migration. Altogether, we present a significantly more detailed view and novel model of early lymphatic development. |
| ISSN | 02614189 |
| Journal | The EMBO Journal |
| Volume Number | 32 |
| PubMed Central reference number | PMC3590982 |
| Issue Number | 5 |
| PubMed reference number | 23299940 |
| e-ISSN | 14602075 |
| DOI | 10.1038/emboj.2012.340 |
| Language | English |
| Publisher | European Molecular Biology Organization |
| Publisher Date | 2013-01-08 |
| Access Restriction | Open |
| Rights License | This article is licensed under a Creative Commons Attribution Noncommercial Share Alike 3.0 Unported License. Copyright © 2013, European Molecular Biology Organization |
| Subject Keyword | lymph vessel development ultramicroscopy VEGFR-3 CCBE1 VEGF-C |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology Molecular Biology |
