Noncanonical protease-activated receptor 1 regulates lymphatic differentiation in zebrafish

Summary: The differentiation of lymphatic progenitors is a crucial step in lymphangiogenesis. However, its underlying mechanism remains unclear. Here, we found that noncanonical protease-activated receptor 1 (par1) regulates the differentiation of lymphatic progenitors in zebrafish embryos. Loss of...

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Autores principales:	Daoxi Lei, Xiuru Zhang, Muhammad Abdul Rouf, Yoga Mahendra, Lin Wen, Yan Li, Xiaojuan Zhang, Li Li, Luming Wang, Tao Zhang, Guixue Wang, Yeqi Wang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Biological sciences Molecular biology Immunology Science Q
Acceso en línea:	https://doaj.org/article/afad1153e4c94cb4b7d25528a14bceac
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spelling	oai:doaj.org-article:afad1153e4c94cb4b7d25528a14bceac2021-11-20T05:11:03ZNoncanonical protease-activated receptor 1 regulates lymphatic differentiation in zebrafish2589-004210.1016/j.isci.2021.103386https://doaj.org/article/afad1153e4c94cb4b7d25528a14bceac2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221013572https://doaj.org/toc/2589-0042Summary: The differentiation of lymphatic progenitors is a crucial step in lymphangiogenesis. However, its underlying mechanism remains unclear. Here, we found that noncanonical protease-activated receptor 1 (par1) regulates the differentiation of lymphatic progenitors in zebrafish embryos. Loss of par1 function impaired lymphatic differentiation by downregulating prox1a expression in parachordal lymphangioblasts and caused compromised thoracic duct formation in zebrafish. Meanwhile, the G protein gnai2a, a par1 downstream effector, was selectively required for lymphatic development in zebrafish, and its mutation mimicked the lymphatic phenotype observed in par1 mutants. Interestingly, mmp13, but not thrombin, was required for lymphatic development in zebrafish. Furthermore, analyses of genetic interactions confirmed that mmp13b serves as a par1 upstream protease to regulate lymphatic development in zebrafish embryos. Mechanistically, par1 promotes flt4 expression and phospho-Erk1/2 activity in the posterior cardinal vein. Taken together, our findings highlight a function of par1 in the regulation of lymphatic differentiation in zebrafish embryos.Daoxi LeiXiuru ZhangMuhammad Abdul RoufYoga MahendraLin WenYan LiXiaojuan ZhangLi LiLuming WangTao ZhangGuixue WangYeqi WangElsevierarticleBiological sciencesMolecular biologyImmunologyScienceQENiScience, Vol 24, Iss 11, Pp 103386- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biological sciences Molecular biology Immunology Science Q
spellingShingle	Biological sciences Molecular biology Immunology Science Q Daoxi Lei Xiuru Zhang Muhammad Abdul Rouf Yoga Mahendra Lin Wen Yan Li Xiaojuan Zhang Li Li Luming Wang Tao Zhang Guixue Wang Yeqi Wang Noncanonical protease-activated receptor 1 regulates lymphatic differentiation in zebrafish
description	Summary: The differentiation of lymphatic progenitors is a crucial step in lymphangiogenesis. However, its underlying mechanism remains unclear. Here, we found that noncanonical protease-activated receptor 1 (par1) regulates the differentiation of lymphatic progenitors in zebrafish embryos. Loss of par1 function impaired lymphatic differentiation by downregulating prox1a expression in parachordal lymphangioblasts and caused compromised thoracic duct formation in zebrafish. Meanwhile, the G protein gnai2a, a par1 downstream effector, was selectively required for lymphatic development in zebrafish, and its mutation mimicked the lymphatic phenotype observed in par1 mutants. Interestingly, mmp13, but not thrombin, was required for lymphatic development in zebrafish. Furthermore, analyses of genetic interactions confirmed that mmp13b serves as a par1 upstream protease to regulate lymphatic development in zebrafish embryos. Mechanistically, par1 promotes flt4 expression and phospho-Erk1/2 activity in the posterior cardinal vein. Taken together, our findings highlight a function of par1 in the regulation of lymphatic differentiation in zebrafish embryos.
format	article
author	Daoxi Lei Xiuru Zhang Muhammad Abdul Rouf Yoga Mahendra Lin Wen Yan Li Xiaojuan Zhang Li Li Luming Wang Tao Zhang Guixue Wang Yeqi Wang
author_facet	Daoxi Lei Xiuru Zhang Muhammad Abdul Rouf Yoga Mahendra Lin Wen Yan Li Xiaojuan Zhang Li Li Luming Wang Tao Zhang Guixue Wang Yeqi Wang
author_sort	Daoxi Lei
title	Noncanonical protease-activated receptor 1 regulates lymphatic differentiation in zebrafish
title_short	Noncanonical protease-activated receptor 1 regulates lymphatic differentiation in zebrafish
title_full	Noncanonical protease-activated receptor 1 regulates lymphatic differentiation in zebrafish
title_fullStr	Noncanonical protease-activated receptor 1 regulates lymphatic differentiation in zebrafish
title_full_unstemmed	Noncanonical protease-activated receptor 1 regulates lymphatic differentiation in zebrafish
title_sort	noncanonical protease-activated receptor 1 regulates lymphatic differentiation in zebrafish
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/afad1153e4c94cb4b7d25528a14bceac
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Noncanonical protease-activated receptor 1 regulates lymphatic differentiation in zebrafish

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