scholarly journals Lymphatic endothelial progenitors bud from the cardinal vein and intersomitic vessels in mammalian embryos

Blood ◽  
2012 ◽  
Vol 120 (11) ◽  
pp. 2340-2348 ◽  
Author(s):  
Ying Yang ◽  
José Manuel García-Verdugo ◽  
Mario Soriano-Navarro ◽  
R. Sathish Srinivasan ◽  
Joshua P. Scallan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Vessels ◽  
Fluid Balance ◽  
Tissue Fluid ◽  
Lymphatic Endothelial Cells ◽  
Cardinal Vein ◽  
Cellular Processes ◽  
Mammalian Embryos ◽  
Lymphatic Vasculature ◽  
Lymphatic Network

Abstract The lymphatic vasculature preserves tissue fluid balance by absorbing fluid and macromolecules and transporting them to the blood vessels for circulation. The stepwise process leading to the formation of the mammalian lymphatic vasculature starts by the expression of the gene Prox1 in a subpopulation of blood endothelial cells (BECs) on the cardinal vein (CV) at approximately E9.5. These Prox1-expressing lymphatic endothelial cells (LECs) will exit the CV to form lymph sacs, primitive structures from which the entire lymphatic network is derived. Until now, no conclusive information was available regarding the cellular processes by which these LEC progenitors exit the CV without compromising the vein's integrity. We determined that LECs leave the CV by an active budding mechanism. During this process, LEC progenitors are interconnected by VE-cadherin–expressing junctions. Surprisingly, we also found that Prox1-expressing LEC progenitors were present not only in the CV but also in the intersomitic vessels (ISVs). Furthermore, as LEC progenitors bud from the CV and ISVs into the surrounding mesenchyme, they begin expressing the lymphatic marker podoplanin, migrate away from the CV, and form the lymph sacs. Analyzing this process in Prox1-null embryos revealed that Prox1 activity is necessary for LEC progenitors to exit the CV.

scholarly journals Liprin β1 is highly expressed in lymphatic vasculature and is important for lymphatic vessel integrity

Blood ◽  
2010 ◽  
Vol 115 (4) ◽  
pp. 906-909 ◽  
Author(s):  
Camilla Norrmén ◽  
Wouter Vandevelde ◽  
Annelii Ny ◽  
Pipsa Saharinen ◽  
Massimiliano Gentile ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lymphatic Vessel ◽  
Lipid Absorption ◽  
Tissue Fluid ◽  
Lymphatic Endothelial Cells ◽  
Isolation And Characterization ◽  
Lymphatic Vasculature ◽  
Vessel Integrity

Abstract The lymphatic vasculature is important for the regulation of tissue fluid homeostasis, immune response, and lipid absorption, and the development of in vitro models should allow for a better understanding of the mechanisms regulating lymphatic vascular growth, repair, and function. Here we report isolation and characterization of lymphatic endothelial cells from human intestine and show that intestinal lymphatic endothelial cells have a related but distinct gene expression profile from human dermal lymphatic endothelial cells. Furthermore, we identify liprin β1, a member of the family of LAR transmembrane tyrosine phosphatase-interacting proteins, as highly expressed in intestinal lymphatic endothelial cells in vitro and lymphatic vasculature in vivo, and show that it plays an important role in the maintenance of lymphatic vessel integrity in Xenopus tadpoles.

scholarly journals Organ-specific lymphatic vasculature: From development to pathophysiology

2017 ◽  
Vol 215 (1) ◽  
pp. 35-49 ◽  
Author(s):  
Tatiana V. Petrova ◽  
Gou Young Koh
Keyword(s):  
Endothelial Cells ◽  
Dietary Fat ◽  
Lymphatic Vessels ◽  
Developmental Origins ◽  
Lymphatic Endothelial Cells ◽  
Tissue Microenvironment ◽  
Organ Specific ◽  
Intestinal Lymphatics ◽  
Lymphatic Vasculature ◽  
Fat Uptake

Recent discoveries of novel functions and diverse origins of lymphatic vessels have drastically changed our view of lymphatic vasculature. Traditionally regarded as passive conduits for fluid and immune cells, lymphatic vessels now emerge as active, tissue-specific players in major physiological and pathophysiological processes. Lymphatic vessels show remarkable plasticity and heterogeneity, reflecting their functional specialization to control the tissue microenvironment. Moreover, alternative developmental origins of lymphatic endothelial cells in some organs may contribute to the diversity of their functions in adult tissues. This review aims to summarize the most recent findings of organotypic differentiation of lymphatic endothelial cells in terms of their distinct (patho)physiological functions in skin, lymph nodes, small intestine, brain, and eye. We discuss recent advances in our understanding of the heterogeneity of lymphatic vessels with respect to the organ-specific functional and molecular specialization of lymphatic endothelium, such as the hybrid blood-lymphatic identity of Schlemm’s canal, functions of intestinal lymphatics in dietary fat uptake, and discovery of meningeal lymphatic vasculature and perivascular brain lymphatic endothelial cells.

scholarly journals Role of synectin in lymphatic development in zebrafish and frogs

Blood ◽  
2010 ◽  
Vol 116 (17) ◽  
pp. 3356-3366 ◽  
Author(s):  
Karlien Hermans ◽  
Filip Claes ◽  
Wouter Vandevelde ◽  
Wei Zheng ◽  
Ilse Geudens ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Thoracic Duct ◽  
Pdz Domain ◽  
Lymphatic Endothelial Cells ◽  
Cardinal Vein ◽  
Morpholino Knockdown ◽  
Lymphatic Development ◽  
Factor C ◽  
Endothelial Growth Factor

Abstract The molecular basis of lymphangiogenesis remains incompletely characterized. Here, we document a novel role for the PDZ domain-containing scaffold protein synectin in lymphangiogenesis using genetic studies in zebrafish and tadpoles. In zebrafish, the thoracic duct arises from parachordal lymphangioblast cells, which in turn derive from secondary lymphangiogenic sprouts from the posterior cardinal vein. Morpholino knockdown of synectin in zebrafish impaired formation of the thoracic duct, due to selective defects in lymphangiogenic but not angiogenic sprouting. Synectin genetically interacted with Vegfr3 and neuropilin-2a in regulating lymphangiogenesis. Silencing of synectin in tadpoles caused lymphatic defects due to an underdevelopment and impaired migration of Prox-1+ lymphatic endothelial cells. Molecular analysis further revealed that synectin regulated Sox18-induced expression of Prox-1 and vascular endothelial growth factor C–induced migration of lymphatic endothelial cells in vitro. These findings reveal a novel role for synectin in lymphatic development.

scholarly journals Meningeal lymphatic endothelial cells fulfill scavenger endothelial cell function and employ Mrc1a for cargo uptake

2019 ◽  
Author(s):  
Yvonne Padberg ◽  
Andreas van Impel ◽  
Max van Lessen ◽  
Jeroen Bussmann ◽  
Stefan Schulte-Merker
Keyword(s):  
Endothelial Cells ◽  
Cell Function ◽  
Molecular Level ◽  
Physiological Role ◽  
Specific Substrate ◽  
Lymphatic Endothelial Cells ◽  
Cardinal Vein ◽  
Endothelial Cell Function ◽  
Surface Receptors ◽  
The Brain

AbstractBrain lymphatic endothelial cells (BLECs) constitute a group of loosely connected endothelial cells within the meningeal layer of the zebrafish brain. We previously reported that BLECs efficiently endocytose extracellular cargo molecules (van Lessen et al., 2017), but how this is accomplished and controlled on the molecular level remains unclear. We here compare BLECs to scavenging endothelial cells (SECs) in the embryonic cardinal vein and find them to accept an identical set of substrate molecules. While there is redundancy in the type of scavenger receptors being used, the two cell populations rely for specific substrate molecules on different cell surface receptors to mediate their physiological role: Stab2 appears more critical within SECs in the cardinal vein, while BLECs depend more on the Mrc1a receptor for internalization of cargo. Given the striking similarities to the substrate specificity of cardinal vein SECs, we postulate that BLECs qualify functionally as SECs of the brain.

scholarly journals Zebrafish prox1b Mutants Develop a Lymphatic Vasculature, and prox1b Does Not Specifically Mark Lymphatic Endothelial Cells

PLoS ONE ◽  
2011 ◽  
Vol 6 (12) ◽  
pp. e28934 ◽  
Author(s):  
Shijie Tao ◽  
Merlijn Witte ◽  
Robert J. Bryson-Richardson ◽  
Peter D. Currie ◽  
Benjamin M. Hogan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lymphatic Endothelial Cells ◽  
Lymphatic Vasculature

scholarly journals When form meets function: the cells and signals that shape the lymphatic vasculature during development

Development ◽  
2021 ◽  
Vol 148 (11) ◽  
Author(s):  
Mathias Francois ◽  
Anna Oszmiana ◽  
Natasha L. Harvey
Keyword(s):  
Network Formation ◽  
Immune Cell ◽  
Lymphatic Endothelial Cell ◽  
Dietary Lipids ◽  
Cell Trafficking ◽  
Tissue Fluid ◽  
Cellular Events ◽  
Formation Function ◽  
Lymphatic Vasculature ◽  
Lymphatic Network

ABSTRACT The lymphatic vasculature is an integral component of the cardiovascular system. It is essential to maintain tissue fluid homeostasis, direct immune cell trafficking and absorb dietary lipids from the digestive tract. Major advances in our understanding of the genetic and cellular events important for constructing the lymphatic vasculature during development have recently been made. These include the identification of novel sources of lymphatic endothelial progenitor cells, the recognition of lymphatic endothelial cell specialisation and heterogeneity, and discovery of novel genes and signalling pathways underpinning developmental lymphangiogenesis. Here, we review these advances and discuss how they inform our understanding of lymphatic network formation, function and dysfunction.

scholarly journals Wasp controls oriented migration of endothelial cells to achieve functional vascular patterning

2020 ◽  
Author(s):  
André Rosa ◽  
Wolfgang Giese ◽  
Katja Meier ◽  
Silvanus Alt ◽  
Alexandra Klaus-Bergmann ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Blood Vessels ◽  
Vascular Malformations ◽  
Cell Movement ◽  
Hierarchical Organization ◽  
Endothelial Cell Migration ◽  
Differential Migration ◽  
Vascular Patterning ◽  
Cellular Processes

AbstractEndothelial cell migration and proliferation are essential for the establishment of a hierarchical organization of blood vessels and optimal distribution of blood. However, how these cellular processes are coordinated remains unknown. Here, using the zebrafish trunk vasculature we show that in future veins endothelial cells proliferate more than in future arteries and migrate preferentially towards neighboring arteries. In future arteries endothelial cells show a biphasic migration profile. During sprouting cells move away from the dorsal aorta, during remodelling cells stop or move towards the feeding aorta. The final morphology of blood vessels is thus established by local proliferation and oriented cell migration to and from neighboring vessels. Additionally, we identify WASp to be essential for this differential migration. Loss of WASp leads to irregular distribution of endothelial cells, substantially enlarged veins and persistent arteriovenous shunting. Mechanistically, we report that WASp drives the assembly of junctional associated actin filaments and is required for junctional expression of PECAM-1. Together, our data identify that functional vascular patterning in the zebrafish trunk utilizes differential cell movement regulated by junctional actin, and that interruption of differential migration may represent a pathomechanism in vascular malformations.

scholarly journals Cell Fate Determination of Lymphatic Endothelial Cells

2020 ◽  
Vol 21 (13) ◽  
pp. 4790
Author(s):  
Young Jae Lee
Keyword(s):  
Endothelial Cells ◽  
Immune Responses ◽  
Cell Fate ◽  
Dietary Fat ◽  
Vascular System ◽  
Lymphatic Endothelial Cells ◽  
Lymphatic Vasculature ◽  
Fat Uptake ◽  
Mammalian System

The lymphatic vasculature, along with the blood vasculature, is a vascular system in our body that plays important functions in fluid homeostasis, dietary fat uptake, and immune responses. Defects in the lymphatic system are associated with various diseases such as lymphedema, atherosclerosis, fibrosis, obesity, and inflammation. The first step in lymphangiogenesis is determining the cell fate of lymphatic endothelial cells. Several genes involved in this commitment step have been identified using animal models, including genetically modified mice. This review provides an overview of these genes in the mammalian system and related human diseases.

T1α/podoplanin is essential for capillary morphogenesis in lymphatic endothelial cells

2008 ◽  
Vol 295 (4) ◽  
pp. L543-L551 ◽  
Author(s):  
Angels Navarro ◽  
Ricardo E. Perez ◽  
Mo Rezaiekhaligh ◽  
Sherry M. Mabry ◽  
Ikechukwu I. Ekekezie
Keyword(s):  
Endothelial Cells ◽  
Capillary Tube ◽  
Transmembrane Protein ◽  
Tube Formation ◽  
Small Gtpase ◽  
Lymph Vessel ◽  
Early Event ◽  
Lymphatic Endothelial Cells ◽  
Podoplanin Expression ◽  
Lymphatic Vasculature

The lymphatic vasculature functions to maintain tissue perfusion homeostasis. Defects in its formation or disruption of the vessels result in lymphedema, the effective treatment of which is hampered by limited understanding of factors regulating lymph vessel formation. Mice lacking T1α/podoplanin, a lymphatic endothelial cell transmembrane protein, have malformed lymphatic vasculature with lymphedema at birth, but the molecular mechanism for this phenotype is unknown. Here, we show, using primary human lung microvascular lymphatic endothelial cells (HMVEC-LLy), that small interfering RNA-mediated silence of podoplanin gene expression has the dramatic effect of blocking capillary tube formation in Matrigel. In addition, localization of phosphorylated ezrin/radixin/moesin proteins to plasma membrane extensions, an early event in the capillary morphogenic program in lymphatic endothelial cells, is impaired. We find that cells with decreased podoplanin expression fail to properly activate the small GTPase RhoA early (by 30 min) after plating on Matrigel, and Rac1 shows a delay in its activation. Further indication that podoplanin action is linked to RhoA activation is that use of a cell-permeable inhibitor of Rho inhibited lymphatic endothelial capillary tube formation in the same manner as did podoplanin gene silencing, which was not mimicked by treatment with a Rac1 inhibitor. These data clearly demonstrate that early activation of RhoA in the lymphangiogenic process, which is required for the successful establishment of the capillary network, is dependent on podoplanin expression. To our knowledge, this is the first time that a mechanism has been suggested to explain the role of podoplanin in lymphangiogenesis.

scholarly journals Ligand-directed targeting of lymphatic vessels uncovers mechanistic insights in melanoma metastasis

2015 ◽  
Vol 112 (8) ◽  
pp. 2521-2526 ◽  
Author(s):  
Dawn R. Christianson ◽  
Andrey S. Dobroff ◽  
Bettina Proneth ◽  
Amado J. Zurita ◽  
Ahmad Salameh ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lymphatic Vessels ◽  
Melanoma Cells ◽  
Cell Interactions ◽  
Melanoma Metastasis ◽  
Lymphatic Endothelium ◽  
Lymphatic Endothelial Cells ◽  
Cell Surfaces ◽  
Surface Binding ◽  
Lymphatic Vasculature

Metastasis is the most lethal step of cancer progression in patients with invasive melanoma. In most human cancers, including melanoma, tumor dissemination through the lymphatic vasculature provides a major route for tumor metastasis. Unfortunately, molecular mechanisms that facilitate interactions between melanoma cells and lymphatic vessels are unknown. Here, we developed an unbiased approach based on molecular mimicry to identify specific receptors that mediate lymphatic endothelial–melanoma cell interactions and metastasis. By screening combinatorial peptide libraries directly on afferent lymphatic vessels resected from melanoma patients during sentinel lymphatic mapping and lymph node biopsies, we identified a significant cohort of melanoma and lymphatic surface binding peptide sequences. The screening approach was designed so that lymphatic endothelium binding peptides mimic cell surface proteins on tumor cells. Therefore, relevant metastasis and lymphatic markers were biochemically identified, and a comprehensive molecular profile of the lymphatic endothelium during melanoma metastasis was generated. Our results identified expression of the phosphatase 2 regulatory subunit A, α-isoform (PPP2R1A) on the cell surfaces of both melanoma cells and lymphatic endothelial cells. Validation experiments showed that PPP2R1A is expressed on the cell surfaces of both melanoma and lymphatic endothelial cells in vitro as well as independent melanoma patient samples. More importantly, PPP2R1A-PPP2R1A homodimers occur at the cellular level to mediate cell–cell interactions at the lymphatic–tumor interface. Our results revealed that PPP2R1A is a new biomarker for melanoma metastasis and show, for the first time to our knowledge, an active interaction between the lymphatic vasculature and melanoma cells during tumor progression.

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