Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
The molecular mechanisms that regulate the earliest steps of lymphatic vascular system development are unknown. To identify regulators of lymphatic competence and commitment, we used an in vitro vascular assay with mouse embryonic stem cell-derived embryoid bodies (EBs). We found that incubation with retinoic acid (RA) and, more potently, with RA in combination with cAMP, induced the expression of the lymphatic competence marker LYVE-1 in the vascular structures of the EBs. This effect was dependent on RA receptor (RAR)-α and protein kinase A signaling. RA-cAMP incubation also promoted the development of CD31+/LYVE-1+/Prox1+ cell clusters. In situ studies revealed that RAR-α is expressed by endothelial cells of the cardinal vein in ED 9.5-11.5 mouse embryos. Timed exposure of mouse and Xenopus embryos to excess of RA upregulated LYVE-1 and VEGFR-3 on embryonic veins and increased formation of Prox1-positive lymphatic progenitors. These findings indicate that RA signaling mediates the earliest steps of lymphatic vasculature development.
???displayArticle.pubmedLink???
21099229
???displayArticle.pmcLink???PMC2997449 ???displayArticle.link???J Vasc Res ???displayArticle.grants???[+]
Abtahian,
Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk.
2003, Pubmed
Abtahian,
Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk.
2003,
Pubmed
Al-Rawi,
The effects of interleukin-7 on the lymphangiogenic properties of human endothelial cells.
2005,
Pubmed
Alitalo,
Lymphangiogenesis in development and human disease.
2005,
Pubmed
Apfel,
A retinoic acid receptor alpha antagonist selectively counteracts retinoic acid effects.
1992,
Pubmed
Banziger-Tobler,
Growth hormone promotes lymphangiogenesis.
2008,
Pubmed
Bermingham-McDonogh,
Expression of Prox1 during mouse cochlear development.
2006,
Pubmed
Björndahl,
Insulin-like growth factors 1 and 2 induce lymphangiogenesis in vivo.
2005,
Pubmed
Brändli,
Molecular cloning of tyrosine kinases in the early Xenopus embryo: identification of Eck-related genes expressed in cranial neural crest cells of the second (hyoid) arch.
1995,
Pubmed
,
Xenbase
Burke,
Prox1 is an early specific marker for the developing liver and pancreas in the mammalian foregut endoderm.
2002,
Pubmed
Bäckhed,
Postnatal lymphatic partitioning from the blood vasculature in the small intestine requires fasting-induced adipose factor.
2007,
Pubmed
Cañón,
Rapid effects of retinoic acid on CREB and ERK phosphorylation in neuronal cells.
2004,
Pubmed
Chan,
Maternal diabetes increases the risk of caudal regression caused by retinoic acid.
2002,
Pubmed
Clagett-Dame,
The role of vitamin A in mammalian reproduction and embryonic development.
2002,
Pubmed
Cueni,
The lymphatic system in health and disease.
2008,
Pubmed
Dawid,
Xenopus laevis in developmental and molecular biology.
1988,
Pubmed
,
Xenbase
Drab,
From totipotent embryonic stem cells to spontaneously contracting smooth muscle cells: a retinoic acid and db-cAMP in vitro differentiation model.
1997,
Pubmed
Dudas,
Prospero-related homeobox 1 (Prox1) is a stable hepatocyte marker during liver development, injury and regeneration, and is absent from "oval cells".
2006,
Pubmed
Duester,
Retinoic acid synthesis and signaling during early organogenesis.
2008,
Pubmed
Dyer,
Regulation of proliferation, cell fate specification and differentiation by the homeodomain proteins Prox1, Six3, and Chx10 in the developing retina.
2003,
Pubmed
François,
Sox18 induces development of the lymphatic vasculature in mice.
2008,
Pubmed
Gaetano,
Retinoids induce fibroblast growth factor-2 production in endothelial cells via retinoic acid receptor alpha activation and stimulate angiogenesis in vitro and in vivo.
2001,
Pubmed
Gaillard,
Phosphorylation by PKA potentiates retinoic acid receptor alpha activity by means of increasing interaction with and phosphorylation by cyclin H/cdk7.
2006,
Pubmed
Gale,
Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by Angiopoietin-1.
2002,
Pubmed
Gale,
Normal lymphatic development and function in mice deficient for the lymphatic hyaluronan receptor LYVE-1.
2007,
Pubmed
Hatzopoulos,
Isolation and characterization of endothelial progenitor cells from mouse embryos.
1998,
Pubmed
Helbling,
Requirement for EphA receptor signaling in the segregation of Xenopus third and fourth arch neural crest cells.
1998,
Pubmed
,
Xenbase
Helbling,
Comparative analysis of embryonic gene expression defines potential interaction sites for Xenopus EphB4 receptors with ephrin-B ligands.
1999,
Pubmed
,
Xenbase
Hirakawa,
VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis.
2005,
Pubmed
Hirakawa,
VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites.
2007,
Pubmed
Huang,
CRSBP-1/LYVE-l-null mice exhibit identifiable morphological and functional alterations of lymphatic capillary vessels.
2006,
Pubmed
Jurisic,
Lymphatic endothelium in health and disease.
2009,
Pubmed
Karkkainen,
Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins.
2004,
Pubmed
Kerjaschki,
Lymphatic neoangiogenesis in renal transplants: a driving force of chronic rejection?
2006,
Pubmed
Kochhar,
Teratogenic activity of retinoic acid.
1967,
Pubmed
Koide,
Active repression of RAR signaling is required for head formation.
2001,
Pubmed
,
Xenbase
Kreuger,
Early lymph vessel development from embryonic stem cells.
2006,
Pubmed
Kurosawa,
Methods for inducing embryoid body formation: in vitro differentiation system of embryonic stem cells.
2007,
Pubmed
Kälin,
An in vivo chemical library screen in Xenopus tadpoles reveals novel pathways involved in angiogenesis and lymphangiogenesis.
2009,
Pubmed
,
Xenbase
Lang,
States of developmental commitment of a mouse embryonal carcinoma cell line differentiating along a neural pathway.
1989,
Pubmed
Liersch,
Induction of lymphatic endothelial cell differentiation in embryoid bodies.
2006,
Pubmed
Lingen,
Inhibition of squamous cell carcinoma angiogenesis by direct interaction of retinoic acid with endothelial cells.
1996,
Pubmed
Lohnes,
Developmental roles of the retinoic acid receptors.
1995,
Pubmed
Majewski,
Retinoids, interferon alpha, 1,25-dihydroxyvitamin D3 and their combination inhibit angiogenesis induced by non-HPV-harboring tumor cell lines. RAR alpha mediates the antiangiogenic effect of retinoids.
1995,
Pubmed
Manshouri,
Downregulation of RAR alpha in mice by antisense transgene leads to a compensatory increase in RAR beta and RAR gamma and development of lymphoma.
1997,
Pubmed
Molotkov,
Retinoic acid generated by Raldh2 in mesoderm is required for mouse dorsal endodermal pancreas development.
2005,
Pubmed
Moro Balbás,
Retinoic acid induces changes in the rhombencephalic neural crest cells migration and extracellular matrix composition in chick embryos.
1993,
Pubmed
Mäkinen,
PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature.
2005,
Pubmed
Ny,
A genetic Xenopus laevis tadpole model to study lymphangiogenesis.
2005,
Pubmed
,
Xenbase
Ogura,
Postnatal changes in gene expression of retinal dehydrogenase and retinoid receptors in liver of rats.
2004,
Pubmed
Oikawa,
A highly potent antiangiogenic activity of retinoids.
1989,
Pubmed
Oliver,
Lymphatic vasculature development.
2004,
Pubmed
Ozeki,
Developmental eye abnormalities in mouse fetuses induced by retinoic acid.
1998,
Pubmed
Petrova,
Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis.
2004,
Pubmed
Quemelo,
Teratogenic effect of retinoic acid in swiss mice.
2007,
Pubmed
Radhika,
Effects of vitamin A deficiency during pregnancy on maternal and child health.
2002,
Pubmed
Rinderknecht,
Tumor lymphangiogenesis and melanoma metastasis.
2008,
Pubmed
Saito,
All-trans retinoic acid induces in vitro angiogenesis via retinoic acid receptor: possible involvement of paracrine effects of endogenous vascular endothelial growth factor signaling.
2007,
Pubmed
Saulnier,
Essential function of Wnt-4 for tubulogenesis in the Xenopus pronephric kidney.
2002,
Pubmed
,
Xenbase
Schacht,
T1alpha/podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema.
2003,
Pubmed
Sebzda,
Syk and Slp-76 mutant mice reveal a cell-autonomous hematopoietic cell contribution to vascular development.
2006,
Pubmed
Shimoda,
Abnormal recruitment of periendothelial cells to lymphatic capillaries in digestive organs of angiopoietin-2-deficient mice.
2007,
Pubmed
Srinivasan,
Lineage tracing demonstrates the venous origin of the mammalian lymphatic vasculature.
2007,
Pubmed
Taniguchi,
Spreds are essential for embryonic lymphangiogenesis by regulating vascular endothelial growth factor receptor 3 signaling.
2007,
Pubmed
Tomarev,
Chicken homeobox gene Prox 1 related to Drosophila prospero is expressed in the developing lens and retina.
1996,
Pubmed
White,
Defects in embryonic hindbrain development and fetal resorption resulting from vitamin A deficiency in the rat are prevented by feeding pharmacological levels of all-trans-retinoic acid.
1998,
Pubmed
White,
Abnormal development of the sinuatrial venous valve and posterior hindbrain may contribute to late fetal resorption of vitamin A-deficient rat embryos.
2000,
Pubmed
Wigle,
Prox1 function is crucial for mouse lens-fibre elongation.
1999,
Pubmed
Wigle,
An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype.
2002,
Pubmed
Wilting,
Lymphangioblasts in embryonic lymphangiogenesis.
2003,
Pubmed
Wilting,
Development of the avian lymphatic system.
2001,
Pubmed
Yuan,
Abnormal lymphatic vessel development in neuropilin 2 mutant mice.
2002,
Pubmed
Zhao,
Differentiation of embryonic stem cells into retinal neurons.
2002,
Pubmed