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

Citation

Cha, Boksik et al. (2020), YAP and TAZ maintain PROX1 expression in the developing lymphatic and lymphovenous valves in response to VEGF-C signaling, Dryad, Dataset, https://doi.org/10.5061/dryad.ncjsxkst1

Abstract

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/TAZ as a critical molecular pathway in valve development.

Methods

Primary human lymphatic endothelial cells were treated with 20µM VP for 2 hours. RNA was subjected to ribosomal RNA depletion followed by Truseq stranded total RNA library preparation according to the manufacturer’s instruction (Illumina). The resulting RNA-seq libraries were analyzed on the Illumina HiSeq sequencing platform.

Usage Notes

The entire dataset is provided.

Funding

National Heart, Lung, and Blood Institute, Award: R01HL131652

National Institute of General Medical Sciences, Award: P20 GM103441

National Heart, Lung, and Blood Institute, Award: R01HL133216

National Research Foundation of Korea, Award: 2020R1F1A1060680

American Heart Association, Award: 19POST34380819