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

Boksik Cha, Yen Chun Ho, Xin Geng, Md Riaj Mahamud, Lijuan Chen, Yeunhee Kim, Dongwon Choi, Tae Hoon Kim, Gwendalyn J. Randolph, Xinwei Cao, Hong Chen, R. Sathish Srinivasan

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 and TAZ as a crucial molecular pathway in valve development.

Original languageEnglish
Article numberdev195453
JournalDevelopment (Cambridge)
Volume147
Issue number23
DOIs
StatePublished - Dec 2020

Keywords

  • Lymphovenous valves
  • PROX1
  • TAZ
  • VEGF-C
  • Valves
  • YAP

Fingerprint

Dive into the research topics of 'YAP and TAZ maintain PROX1 expression in the developing lymphatic and lymphovenous valves in response to VEGF-C signaling'. Together they form a unique fingerprint.

Cite this