Complementary Wnt Sources Regulate Lymphatic Vascular Development via PROX1-Dependent Wnt/β-Catenin Signaling

被引：61

作者：

Cha, Boksik ^{[1
]}

Geng, Xin ^{[1
]}

Mahamud, Md. Riaj ^{[1
,2
]}

Zhang, Jenny Y. ^{[3
]}

Chen, Lijuan ^{[1
]}

Kim, Wantae ^{[4
]}

Jho, Eek-Hoon ^{[5
]}

Kim, Yeunhee ^{[6
,7
]}

Choi, Dongwon ^{[8
]}

Dixon, J. Brandon ^{[9
]}

Chen, Hong ^{[10
]}

Hong, Young-Kwon ^{[8
]}

Olson, Lorin ^{[1
,2
]}

Kim, Tae Hoon ^{[6
,7
]}

Merrill, Bradley J. ^{[3
]}

Davis, Michael J. ^{[11
]}

Srinivasan, R. Sathish ^{[1
,2
]}

机构：

[1] Oklahoma Med Res Fdn, Cardiovasc Biol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA

[2] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK USA

[3] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL USA

[4] KRIBB, Rare Dis Res Ctr, Deajeon, South Korea

[5] Univ Seoul, Dept Life Sci, Seoul, South Korea

[6] Univ Texas Dallas, Dept Biol Sci, Richardson, TX 75083 USA

[7] Univ Texas Dallas, Ctr Syst Biol, Richardson, TX 75083 USA

[8] Univ Southern Calif, Keck Sch Med, Los Angeles, CA USA

[9] Georgia Inst Technol, Parker H Petit Inst Bioengn & Biosci, Atlanta, GA 30332 USA

[10] Boston Childrens Hosp, Vasc Biol Program, Boston, MA USA

[11] Univ Missouri, Dept Med Pharmacol & Physiol, Columbia, MO USA

来源：

CELL REPORTS | 2018年 / 25卷 / 03期

基金：

新加坡国家研究基金会;

关键词：

TRANSCRIPTIONAL ACTIVATION; ENDOTHELIAL-CELLS; PROX1; EXPRESSION; MAINTENANCE; LYMPHEDEMA; IDENTITY; DEFECTS; VALVES; FOXC2; MICE;

D O I：

10.1016/j.celrep.2018.09.049

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Wnt/beta-catenin signaling is necessary for lymphatic vascular development. Oscillatory shear stress (OSS) enhances Wnt/beta-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/beta-catenin signaling and GATA2 and FOXC2 expression are unknown. We show that OSS activates autocrine Wnt/beta-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 beta-catenin and the TCF/LEF transcription factor TCF7L1 to enhance Wnt/beta-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.

引用

页码：571 / +

页数：19

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