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Wnt/β-catenin signaling is necessary for lymphatic vascular development. Oscillatory shear stress (OSS) enhances Wnt/β-catenin signaling in cultured lymphatic endothelial cells (LECs) to induce expression of the lymphedema-associated transcription factors GATA2 and FOXC2. However, the mechanisms by which OSS regulates Wnt/β-catenin signaling and GATA2 and FOXC2 expression are unknown. We show that OSS activates autocrine Wnt/β-catenin signaling in LECs in vitro. Tissue-specific deletion of Wntless, which is required for the secretion of Wnt ligands, reveals that LECs and vascular smooth muscle cells are complementary sources of Wnt ligands that regulate lymphatic vascular development in vivo. Further, the LEC master transcription factor PROX1 forms a complex with β-catenin and the TCF/LEF transcription factor TCF7L1 to enhance Wnt/β-catenin signaling and promote FOXC2 and GATA2 expression in LECs. Thus, our work defines Wnt sources, reveals that PROX1 directs cell fate by acting as a Wnt signaling component, and dissects the mechanisms of PROX1 and Wnt synergy.
Pubmed ID: 30332639 RIS Download
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View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HUVEC-C is a Finite cell line with a species of origin Homo sapiens
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis polyclonal targets Rabbit IgG
View all literature mentionsThis polyclonal targets Mouse IgG
View all literature mentionsThis polyclonal targets donkey anti-goat IgG-HRP
View all literature mentionsThis polyclonal targets Sheep IgG
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis polyclonal targets goat IgG
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis polyclonal targets Sheep IgG (H+L)
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis polyclonal targets Mouse VEGF R3 / Flt-4
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal targets Phospho-LRP6 (Ser1490)
View all literature mentionsThis monoclonal targets Catenin, beta
View all literature mentionsThis monoclonal targets slightly modified β-cytoplasmic actin N-terminal peptide, Ac-Asp-Asp-Asp-Ile-Ala-Ala-Leu-Val-Ile-Asp-Asn-Gly-Ser-Gly-Lys, conjugated to KLH
View all literature mentionsThis monoclonal targets Actin alpha-Smooth Muscle - Cy3(TM) antibody produced in mouse
View all literature mentionsThis monoclonal targets Endomucin
View all literature mentionsThis monoclonal targets 129/Sv mouse-derived endothelioma cell line tEnd.1
View all literature mentionsThis polyclonal targets Mouse VEGF R3 / Flt-4
View all literature mentionsThis unknown targets Mouse FoxC2 Affinity Purified Ab
View all literature mentionsThis polyclonal targets Human Prox1
View all literature mentionsThis unknown targets prox1a in the nucleus of lymphatic endothelial cells
View all literature mentionsMus musculus with name B6;129P2-Lyve1tm1.1(EGFP/cre)Cys/J from IMSR.
View all literature mentionsMus musculus with name B6;129S-Lrp6tm1.1Vari/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Tg(Tagln-cre)1Her/J from IMSR.
View all literature mentionsMus musculus with name 129S-Wlstm1.1Lan/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/J from IMSR.
View all literature mentionsMus musculus with name B6;129-Lrp5tm1.1Vari/J from IMSR.
View all literature mentionsMus musculus with name B6.129-Ctnnb1tm2Kem/KnwJ from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Tg(Tek-cre)1Ywa/J from IMSR.
View all literature mentionsThis unknown targets Mouse FoxC2 Affinity Purified Ab
View all literature mentionsThis unknown targets prox1a in the nucleus of lymphatic endothelial cells
View all literature mentionsThis polyclonal targets Human Prox1
View all literature mentionsThis polyclonal targets Mouse VEGF R3 / Flt-4
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsMus musculus with name B6;129-Lrp5tm1.1Vari/J from IMSR.
View all literature mentionsThis polyclonal targets Phospho-LRP6 (Ser1490)
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets slightly modified β-cytoplasmic actin N-terminal peptide, Ac-Asp-Asp-Asp-Ile-Ala-Ala-Leu-Val-Ile-Asp-Asn-Gly-Ser-Gly-Lys, conjugated to KLH
View all literature mentionsThis monoclonal targets Actin alpha-Smooth Muscle - Cy3(TM) antibody produced in mouse
View all literature mentionsThis monoclonal targets Catenin, beta
View all literature mentionsThis monoclonal targets Endomucin
View all literature mentionsThis monoclonal targets 129/Sv mouse-derived endothelioma cell line tEnd.1
View all literature mentionsThis polyclonal targets Mouse VEGF R3 / Flt-4
View all literature mentionsMus musculus with name B6.Cg-Tg(Tek-cre)1Ywa/J from IMSR.
View all literature mentionsMus musculus with name 129S-Wlstm1.1Lan/J from IMSR.
View all literature mentionsThis polyclonal targets goat IgG
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis polyclonal targets Sheep IgG (H+L)
View all literature mentionsThis polyclonal targets Sheep IgG
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsMus musculus with name B6;129P2-Lyve1tm1.1(EGFP/cre)Cys/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Tg(Tagln-cre)1Her/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/J from IMSR.
View all literature mentionsMus musculus with name B6;129S-Lrp6tm1.1Vari/J from IMSR.
View all literature mentionsMus musculus with name B6;129P2-Lyve1tm1.1(EGFP/cre)Cys/J from IMSR.
View all literature mentionsMus musculus with name B6;129S-Lrp6tm1.1Vari/J from IMSR.
View all literature mentionsMus musculus with name 129S-Wlstm1.1Lan/J from IMSR.
View all literature mentionsMus musculus with name B6;129-Lrp5tm1.1Vari/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/J from IMSR.
View all literature mentionsThis polyclonal targets donkey anti-goat IgG-HRP
View all literature mentionsMus musculus with name B6.Cg-Tg(Tagln-cre)1Her/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Tg(Tek-cre)1Ywa/J from IMSR.
View all literature mentionsThis polyclonal targets Rabbit IgG
View all literature mentionsMus musculus with name B6.129-Ctnnb1tm2Kem/KnwJ from IMSR.
View all literature mentionsMus musculus with name B6.129-Ctnnb1tm2Kem/KnwJ from IMSR.
View all literature mentionsThis polyclonal targets Mouse IgG
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