Cargando…

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 PROX...

Descripción completa

Detalles Bibliográficos
Autores principales: Cha, Boksik, Ho, Yen-Chun, Geng, Xin, Mahamud, Md. Riaj, Chen, Lijuan, Kim, Yeunhee, Choi, Dongwon, Kim, Tae Hoon, Randolph, Gwendalyn J., Cao, Xinwei, Chen, Hong, Srinivasan, R. Sathish
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758626/
https://www.ncbi.nlm.nih.gov/pubmed/33060128
http://dx.doi.org/10.1242/dev.195453
_version_ 1783626982153519104
author Cha, Boksik
Ho, Yen-Chun
Geng, Xin
Mahamud, Md. Riaj
Chen, Lijuan
Kim, Yeunhee
Choi, Dongwon
Kim, Tae Hoon
Randolph, Gwendalyn J.
Cao, Xinwei
Chen, Hong
Srinivasan, R. Sathish
author_facet Cha, Boksik
Ho, Yen-Chun
Geng, Xin
Mahamud, Md. Riaj
Chen, Lijuan
Kim, Yeunhee
Choi, Dongwon
Kim, Tae Hoon
Randolph, Gwendalyn J.
Cao, Xinwei
Chen, Hong
Srinivasan, R. Sathish
author_sort Cha, Boksik
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7758626
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher The Company of Biologists Ltd
record_format MEDLINE/PubMed
spelling pubmed-77586262020-12-30 YAP and TAZ maintain PROX1 expression in the developing lymphatic and lymphovenous valves in response to VEGF-C signaling Cha, Boksik Ho, Yen-Chun Geng, Xin Mahamud, Md. Riaj Chen, Lijuan Kim, Yeunhee Choi, Dongwon Kim, Tae Hoon Randolph, Gwendalyn J. Cao, Xinwei Chen, Hong Srinivasan, R. Sathish Development Research Article 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. The Company of Biologists Ltd 2020-12-13 /pmc/articles/PMC7758626/ /pubmed/33060128 http://dx.doi.org/10.1242/dev.195453 Text en © 2020. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Cha, Boksik
Ho, Yen-Chun
Geng, Xin
Mahamud, Md. Riaj
Chen, Lijuan
Kim, Yeunhee
Choi, Dongwon
Kim, Tae Hoon
Randolph, Gwendalyn J.
Cao, Xinwei
Chen, Hong
Srinivasan, R. Sathish
YAP and TAZ maintain PROX1 expression in the developing lymphatic and lymphovenous valves in response to VEGF-C signaling
title YAP and TAZ maintain PROX1 expression in the developing lymphatic and lymphovenous valves in response to VEGF-C signaling
title_full YAP and TAZ maintain PROX1 expression in the developing lymphatic and lymphovenous valves in response to VEGF-C signaling
title_fullStr YAP and TAZ maintain PROX1 expression in the developing lymphatic and lymphovenous valves in response to VEGF-C signaling
title_full_unstemmed YAP and TAZ maintain PROX1 expression in the developing lymphatic and lymphovenous valves in response to VEGF-C signaling
title_short YAP and TAZ maintain PROX1 expression in the developing lymphatic and lymphovenous valves in response to VEGF-C signaling
title_sort yap and taz maintain prox1 expression in the developing lymphatic and lymphovenous valves in response to vegf-c signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758626/
https://www.ncbi.nlm.nih.gov/pubmed/33060128
http://dx.doi.org/10.1242/dev.195453
work_keys_str_mv AT chaboksik yapandtazmaintainprox1expressioninthedevelopinglymphaticandlymphovenousvalvesinresponsetovegfcsignaling
AT hoyenchun yapandtazmaintainprox1expressioninthedevelopinglymphaticandlymphovenousvalvesinresponsetovegfcsignaling
AT gengxin yapandtazmaintainprox1expressioninthedevelopinglymphaticandlymphovenousvalvesinresponsetovegfcsignaling
AT mahamudmdriaj yapandtazmaintainprox1expressioninthedevelopinglymphaticandlymphovenousvalvesinresponsetovegfcsignaling
AT chenlijuan yapandtazmaintainprox1expressioninthedevelopinglymphaticandlymphovenousvalvesinresponsetovegfcsignaling
AT kimyeunhee yapandtazmaintainprox1expressioninthedevelopinglymphaticandlymphovenousvalvesinresponsetovegfcsignaling
AT choidongwon yapandtazmaintainprox1expressioninthedevelopinglymphaticandlymphovenousvalvesinresponsetovegfcsignaling
AT kimtaehoon yapandtazmaintainprox1expressioninthedevelopinglymphaticandlymphovenousvalvesinresponsetovegfcsignaling
AT randolphgwendalynj yapandtazmaintainprox1expressioninthedevelopinglymphaticandlymphovenousvalvesinresponsetovegfcsignaling
AT caoxinwei yapandtazmaintainprox1expressioninthedevelopinglymphaticandlymphovenousvalvesinresponsetovegfcsignaling
AT chenhong yapandtazmaintainprox1expressioninthedevelopinglymphaticandlymphovenousvalvesinresponsetovegfcsignaling
AT srinivasanrsathish yapandtazmaintainprox1expressioninthedevelopinglymphaticandlymphovenousvalvesinresponsetovegfcsignaling