scholarly journals lyve1 expression reveals novel lymphatic vessels and new mechanisms for lymphatic vessel development in zebrafish

Development ◽  
2012 ◽  
Vol 139 (13) ◽  
pp. 2381-2391 ◽  
Author(s):  
K. S. Okuda ◽  
J. W. Astin ◽  
J. P. Misa ◽  
M. V. Flores ◽  
K. E. Crosier ◽  
...  
Keyword(s):  
Lymphatic Vessel ◽  
Lymphatic Vessels ◽  
Vessel Development

scholarly journals S1P-S1PR1 activity controls VEGF-A signaling during lymphatic vessel development

2019 ◽  
Author(s):  
AM Golding-Ochsenbein ◽  
S Vidal ◽  
B Wilmering Wetter ◽  
C Guibourdenche ◽  
C Beerli ◽  
...  
Keyword(s):  
Lymphatic Vessel ◽  
Lymphatic Vessels ◽  
Signaling Crosstalk ◽  
Balanced Growth ◽  
Sphingosine 1 Phosphate ◽  
Genetic Deletion ◽  
Vessel Development ◽  
Perinuclear Area

AbstractSphingosine-1-phosphate (S1P), a lipid signaling molecule produced by endothelial cells, is required for development and homeostasis of blood vessels. However, its role during lymphatic vessel development is unclear. We show in murine newborns that pharmacologically enhanced S1P signaling increases VEGF-A-dependent LEC proliferation. In contrast, S1PR1 inhibition, mediated by the antagonist NIBR0213 or LEC-specific genetic deletion of S1pr1, promotes filopodia formation and vessel branching, independent of VEGF-A. To investigate the S1P and VEGF-A signaling crosstalk observed in vivo, we used LECs cultured in vitro. We demonstrate that S1P activates endogenous S1PR1 in a constitutive, autocrine manner. Importantly, S1P-S1PR1 activity was required for VEGF-A-induced LEC proliferation and strongly supported ERK1/2 activation and VEGFR-2 trafficking to the perinuclear area. In conclusion, S1P-S1PR1 signaling promotes VEGF-A-dependent LEC proliferation and limits migratory and filopodia-forming responses. Hence, S1P-S1PR1 signaling is required for balanced growth factor-induced lymphangiogenesis and correctly patterned lymphatic vessels during postnatal development.

scholarly journals Tbx1 regulates Vegfr3 and is required for lymphatic vessel development

2010 ◽  
Vol 189 (3) ◽  
pp. 417-424 ◽  
Author(s):  
Li Chen ◽  
Annalisa Mupo ◽  
Tuong Huynh ◽  
Sara Cioffi ◽  
Matthew Woods ◽  
...  
Keyword(s):  
Lymphatic Vessel ◽  
Perinatal Death ◽  
Major Gene ◽  
Critical Role ◽  
Lymphatic Vessels ◽  
Enhancer Element ◽  
Conditional Deletion ◽  
Tumor Lymphangiogenesis ◽  
Vessel Network ◽  
Vessel Development

Lymphatic dysfunction causes several human diseases, and tumor lymphangiogenesis is implicated in cancer spreading. TBX1 is the major gene for DiGeorge syndrome, which is associated with multiple congenital anomalies. Mutation of Tbx1 in mice recapitulates the human disease phenotype. In this study, we use molecular, cellular, and genetic approaches to show, unexpectedly, that Tbx1 plays a critical role in lymphatic vessel development and regulates the expression of Vegfr3, a gene that is essential for lymphangiogenesis. Tbx1 activates Vegfr3 transcription in endothelial cells (ECs) by binding to an enhancer element in the Vegfr3 gene. Conditional deletion of Tbx1 in ECs causes widespread lymphangiogenesis defects in mouse embryos and perinatal death. Using the mesentery as a model tissue, we show that Tbx1 is not required for lymphatic EC differentiation; rather, it is required for the growth and maintenance of lymphatic vessels. Our findings reveal a novel pathway for the development of the lymphatic vessel network.

scholarly journals REVIEW OF THE FUNCTION OF SEMA3A IN LYMPHATIC VESSEL MATURATION AND ITS POTENTIAL AS A CANDIDATE GENE FOR LYMPHEDEMA: ANALYSIS OF THREE FAMILIES WITH RARE CAUSATIVE VARIANTS

Lymphology ◽  
2020 ◽  
Vol 53 (2) ◽  
Author(s):  
M Ricci ◽  
C Daolio ◽  
B Amato ◽  
S Kenanoglu ◽  
D Veselenyiova ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Candidate Gene ◽  
Protein Interactions ◽  
Lymphatic Vessel ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Wild Type ◽  
Neuropilin 1 ◽  
Vessel Maturation ◽  
Vessel Development

SEMA3A is a semaphorin involved in cell signaling with PlexinA1 and Neuropilin-1 (NRP1) receptors and it is responsible for recruiting dendritic cells into lymphatics. Mutations in the SEMA3A gene result in abnormalities in lymphatic vessel development and maturation. We investigated the association of SEMA3A variants detected in lymphedema patients with lymphatic maturation and lymphatic system malfunction. First, we used NGS technology to sequence the SEMA3A gene in 235 lymphedema patients who carry wild type alleles for known lymphedema genes. We detected three different missense variants in three families. Bioinformatic results showed that some protein interactions could be altered by these variants. Other unaffected family members of the probands also reported different episodes of subclinical edema. We then evaluated the importance of the SEMA3A gene in the formation and maturation of lymphatic vessels. Our results determined that SEMA3A variants segregate in families with lymphatic system malformations and recommend the inclusion of SEMA3A in the gene panel for testing of patients with lymphedema.

The Notch1-Dll4 signaling pathway regulates mouse postnatal lymphatic development

Blood ◽  
2011 ◽  
Vol 118 (7) ◽  
pp. 1989-1997 ◽  
Author(s):  
Kyle Niessen ◽  
Gu Zhang ◽  
John Brady Ridgway ◽  
Hao Chen ◽  
Ganesh Kolumam ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Lymphatic Vessels ◽  
Mouse Skin ◽  
Notch Signaling Pathway ◽  
Cell Phenotype ◽  
Mural Cell ◽  
Lymphatic Development ◽  
Vessel Development

Abstract The Notch signaling pathway plays a fundamental role during blood vessel development. Notch signaling regulates blood vessel morphogenesis by promoting arterial endothelial differentiation and pro-viding spatial and temporal control over “tip cell” phenotype during angiogenic sprouting. Components of the Notch signaling pathway have emerged as potential regulators of lymphatic development, joining the increasing examples of blood vessel regulators that are also involved in lymphatic development. However, in mammals a role for the Notch signaling pathway during lymphatic development remains to be demonstrated. In this report, we show that blockade of Notch1 and Dll4, with specific function-blocking antibodies, results in defective postnatal lymphatic development in mice. Mechanistically, Notch1-Dll4 blockade is associated with down-regulation of EphrinB2 expression, been shown to be critically involved in VEGFR3/VEGFC signaling, resulting in reduced lymphangiogenic sprouting. In addition, Notch1-Dll4 blockade leads to compromised expression of distinct lymphatic markers and to dilation of collecting lymphatic vessels with reduced and disorganized mural cell coverage. Finally, Dll4-blockade impairs wound closure and severely affects lymphangiogenesis during the wound healing in adult mouse skin. Thus, our study demonstrates for the first time in a mammalian system that Notch1-Dll4 signaling pathway regulates postnatal lymphatic development and pathologic lymphangiogenesis.

Abstract 27: ApoA-I Improves Lymphatic Function Through a Platelet-Dependent Mechanism in Atherosclerotic Mice

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Andreea Milasan ◽  
François Dallaire ◽  
Gabriel Jean ◽  
Jean-Claude Tardif ◽  
Yahye Merhi ◽  
...  
Keyword(s):  
Lymphatic Vessel ◽  
Ex Vivo ◽  
Lymphatic Vessels ◽  
Lymphatic Transport ◽  
Lv Function ◽  
Experimental Conditions ◽  
Lymphatic Function ◽  
Beneficial Effects ◽  
Dependent Mechanism

Rationale: Lymphatic vessels (LVs) are now recognized as prerequisite players in the modulation of cholesterol removal from the artery wall in experimental conditions of plaque regression, and a particular attention has been brought on the role of the collecting LVs in early atherosclerosis-related lymphatic dysfunction. Whereas recent findings revealed that apoA-I restores the neovascularization capacity of the lymphatic system during tumor necrosis factor-induced inflammation, the effect of apoA-I on collecting LV function during atherosclerosis has not been tested. Objective: In the present study, we address whether and how apoA-I can enhance collecting LV function in atherosclerosis-associated lymphatic dysfunction. Methods and Results: A 6-week systemic treatment with lipid-free apoA-I enhanced lymphatic transport and abrogated collecting lymphatic vessel permeability in atherosclerotic Ldlr –/– mice when compared to control. As injection of apoA-I has been shown to protect wild-type mice against flow restriction-induced thrombosis, and that platelets are identified as key elements in the maintenance of lymphatic vessel integrity via their interaction with lymphatic endothelial cells (LECs), we have tested whether the effects of apoA-I could be mediated through a platelet-dependent mechanism. Our in vivo results show that apoA-I kinetics in lymph reflected that of blood. Ex vivo experiments performed with washed platelets isolated from mouse blood reveal that apoA-I decreased thrombin-induced but not podoplanin-induced platelet aggregation. Whereas this result suggests that apoA-I limits platelet thrombotic potential in blood but not in lymph, we demonstrate that treatment of human LECs with apoA-I increases the adhesion of bridge-like platelets on human LECs. Conclusions: Our results suggest that apoA-I can mediate beneficial effects on lymphatic function by promoting platelet adhesion to the lymphatic endothelium and consequently restore collecting LV integrity. Altogether, we bring forward a new pleiotropic role for apoA-I in lymphatic function and unveil new potential therapeutic targets for the prevention and treatment of atherosclerosis.

scholarly journals The cortical actin network regulates avidity-dependent binding of hyaluronan by the lymphatic vessel endothelial receptor LYVE-1

2020 ◽  
Vol 295 (15) ◽  
pp. 5036-5050 ◽  
Author(s):  
Tess A. Stanly ◽  
Marco Fritzsche ◽  
Suneale Banerji ◽  
Dilip Shrestha ◽  
Falk Schneider ◽  
...  
Keyword(s):  
Lymphatic Vessel ◽  
Leukocyte Adhesion ◽  
Lymphatic Vessels ◽  
Super Resolution ◽  
Direct Interaction ◽  
Correlation Spectroscopy ◽  
Stimulated Emission ◽  
Actin Network ◽  
Cortical Actin ◽  
Limited Mobility

Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) mediates the docking and entry of dendritic cells to lymphatic vessels through selective adhesion to its ligand hyaluronan in the leukocyte surface glycocalyx. To bind hyaluronan efficiently, LYVE-1 must undergo surface clustering, a process that is induced efficiently by the large cross-linked assemblages of glycosaminoglycan present within leukocyte pericellular matrices but is induced poorly by the shorter polymer alone. These properties suggested that LYVE-1 may have limited mobility in the endothelial plasma membrane, but no biophysical investigation of these parameters has been carried out to date. Here, using super-resolution fluorescence microscopy and spectroscopy combined with biochemical analyses of the receptor in primary lymphatic endothelial cells, we provide the first evidence that LYVE-1 dynamics are indeed restricted by the submembranous actin network. We show that actin disruption not only increases LYVE-1 lateral diffusion but also enhances hyaluronan-binding activity. However, unlike the related leukocyte HA receptor CD44, which uses ERM and ankyrin motifs within its cytoplasmic tail to bind actin, LYVE-1 displays little if any direct interaction with actin, as determined by co-immunoprecipitation. Instead, as shown by super-resolution stimulated emission depletion microscopy in combination with fluorescence correlation spectroscopy, LYVE-1 diffusion is restricted by transient entrapment within submembranous actin corrals. These results point to an actin-mediated constraint on LYVE-1 clustering in lymphatic endothelium that tunes the receptor for selective engagement with hyaluronan assemblages in the glycocalyx that are large enough to cross-bridge the corral-bound LYVE-1 molecules and thereby facilitate leukocyte adhesion and transmigration.

Angiopoietin-1 promotes lymphatic sprouting and hyperplasia

Blood ◽  
2005 ◽  
Vol 105 (12) ◽  
pp. 4642-4648 ◽  
Author(s):  
Tuomas Tammela ◽  
Anne Saaristo ◽  
Marja Lohela ◽  
Tohru Morisada ◽  
Jenny Tornberg ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Viral Vectors ◽  
Lymphatic Vessels ◽  
Growth Factor Receptor ◽  
Soluble Form ◽  
Tissue Edema ◽  
Mouse Tissues ◽  
Vessel Development ◽  
Endothelial Growth Factor ◽  
Angiopoietin 1

Abstract Angiopoietin 1 (Ang1), a ligand for the receptor tyrosine kinase Tie2, regulates the formation and stabilization of the blood vessel network during embryogenesis. In adults, Ang1 is associated with blood vessel stabilization and recruitment of perivascular cells, whereas Ang2 acts to counter these actions. Recent results from gene-targeted mice have shown that Ang2 is also essential for the proper patterning of lymphatic vessels and that Ang1 can be substituted for this function. In order to characterize the effects of the angiopoietins on lymphatic vessels, we employed viral vectors for overexpression of Ang1 in adult mouse tissues. We found that Ang1 activated lymphatic vessel endothelial proliferation, vessel enlargement, and generation of long endothelial cell filopodia that eventually fused, leading to new sprouts and vessel development. Cutaneous lymphatic hyperplasia was also detected in transgenic mice expressing Ang1 in the basal epidermal cells. Tie2 was expressed in the lymphatic endothelial cells and Ang1 stimulation of these cells resulted in up-regulation of vascular endothelial growth factor receptor 3 (VEGFR-3). Furthermore, a soluble form of VEGFR-3 inhibited the observed lymphatic sprouting. Our results reinforce the concept that Ang1 therapy may be useful in settings of tissue edema. (Blood. 2005;105:4642-4648)

Abnormal lymphatic vessel development is associated with decreased decidual regulatory T cells in severe preeclampsia

2018 ◽  
Vol 80 (1) ◽  
pp. e12970 ◽  
Author(s):  
Yun Ji Jung ◽  
Yejin Park ◽  
Hyun-Soo Kim ◽  
Hwa Jin Lee ◽  
Yoo-Na Kim ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Lymphatic Vessel ◽  
Severe Preeclampsia ◽  
Vessel Development
Sign in / Sign up

Export Citation Format

Share Document