Open AccessYAP and TAZ maintain PROX1 expression in the developing lymphatic and lymphovenous valves in response to VEGF-C signaling
Author(s) -
Boksik Cha,
YenChun Ho,
Xin Geng,
Md. Riaj Mahamud,
Lijuan Chen,
Yeunhee Kim,
Dongwon Choi,
Tae Hoon Kim,
Gwendalyn J. Randolph,
Xinwei Cao,
Hong Chen,
Ramesh Srinivasan
Publication year - 2020
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.195453
Subject(s) - lymphatic system , biology , lymphatic endothelium , vascular endothelial growth factor c , microbiology and biotechnology , transcription factor , lymphangiogenesis , signal transduction , homeobox , vascular endothelial growth factor , morphogenesis , lymphatic vessel , cancer research , vegf receptors , vascular endothelial growth factor a , immunology , gene , cancer , genetics , metastasis
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.