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Title 

Complementary Wnt sources regulate lymphatic vascular development via PROX1-dependent Wnt/b-catenin signaling

 

상보적인 Wnt 소스가 PROX1 의존적으로 Wnt/β-Catenin 신호를 통해 림프 혈관을 조절

Authors 

B ChaX GengM R MahamudJ Y ZhangL ChenWantae KimE H JhoY KimD ChoiJ B DixonH ChenY K HongL OlsonT H KimB J MerrillM J DavisR S Srinivasan

Publisher 

Elsevier

Issue Date 

2018

Citation 

Cell Reports

Keywords 

FOXC2GATA2PROX1TCF7L1Wnt/β-catenin signalingWntlesslymphatic valveslymphatic vasculaturelymphovenous valvesoscillatory shear stress

Abstract 

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.

ISSN 

2211-1247

Link 

http://dx.doi.org/10.1016/j.celrep.2018.09.049

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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