YAP and TAZ maintain PROX1 expression in the developing lymphatic and lymphovenous valves in response to VEGF-C signaling.

Lymphatic vasculature is an integral part of digestive, immune and circulatory systems. The homeobox transcription factor PROX1 is necessary for the development of lymphatic vessels, lymphatic valves (LVs) and lymphovenous valves (LVVs). We and others previously reported a feedback loop between PROX1 and vascular endothelial growth factor-C (VEGF-C) signaling. PROX1 promotes the expression of the VEGF-C receptor VEGFR3 in lymphatic endothelial cells (LECs). In turn, VEGF-C signaling maintains PROX1 expression in LECs. However, the mechanisms of PROX1/VEGF-C feedback loop remain poorly understood. Whether VEGF-C signaling is necessary for LV and LVV development is also unknown. Here, we report for the first time that VEGF-C signaling is necessary for valve morphogenesis. We have also discovered that the transcriptional co-activators YAP and TAZ are required to maintain PROX1 expression in LVs and LVVs in response to VEGF-C signaling. Deletion of Yap and Taz in the lymphatic vasculature of mouse embryos did not affect the formation of LVs or LVVs, but resulted in the degeneration of these structures. Our results have identified VEGF-C, YAP and TAZ as a crucial molecular pathway in valve development.

Cha B ，Ho YC ，Geng X ，Mahamud MR ，Chen L ，Kim Y ，Choi D ，Kim TH ，Randolph GJ ，Cao X ，Chen H ，Srinivasan RS ... -  《-》

YAP and TAZ Negatively Regulate Prox1 During Developmental and Pathologic Lymphangiogenesis.

Cho H ，Kim J ，Ahn JH ，Hong YK ，Mäkinen T ，Lim DS ，Koh GY ... -  《-》

Nicotine enhances the stemness and tumorigenicity in intestinal stem cells via Hippo-YAP/TAZ and Notch signal pathway.

Cigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited. In this study, we demonstrate that NIC increases the abundance and proliferative activity of murine intestinal stem cells (ISCs) in vivo and ex vivo. Moreover, NIC induces Yes-associated protein (YAP) /Transcriptional coactivator with PDZ-binding motif (TAZ) and Notch signaling in ISCs via α7-nicotinic acetylcholine receptor (nAchR) and protein kinase C (PKC) activation; this effect was not detected in Paneth cells. The inhibition of Notch signaling by dibenzazepine (DBZ) nullified the effects of NIC on ISCs. NIC enhances in vivo tumor formation from ISCs after loss of the tumor suppressor gene Apc, DBZ inhibited NIC-induced tumor growth. Hence, this study identifies a NIC-triggered pathway regulating the stemness and tumorigenicity of ISCs and suggests the use of DBZ as a potential therapeutic strategy for treating intestinal tumors.

Isotani R ，Igarashi M ，Miura M ，Naruse K ，Kuranami S ，Katoh M ，Nomura S ，Yamauchi T ... -  《eLife》

PROX1 Inhibits PDGF-B Expression to Prevent Myxomatous Degeneration of Heart Valves.

Ho YC ，Geng X ，O'Donnell A ，Ibarrola J ，Fernandez-Celis A ，Varshney R ，Subramani K ，Azartash-Namin ZJ ，Kim J ，Silasi R ，Wylie-Sears J ，Alvandi Z ，Chen L ，Cha B ，Chen H ，Xia L ，Zhou B ，Lupu F ，Burkhart HM ，Aikawa E ，Olson LE ，Ahamed J ，López-Andrés N ，Bischoff J ，Yutzey KE ，Srinivasan RS ... -  《-》

VEGFC Overexpression in Kidney Progenitor Cells Is a Model of Renal Lymphangiectasia-Brief Report.

Donnan MD ，Deb DK ，Dalal V ，David V ，Procissi D ，Quaggin SE ... -  《-》