摘要：SummaryThe 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 ofpar1function impaired lymphatic differentiation by downregulatingprox1aexpression in parachordal lymphangioblasts and caused compromised thoracic duct formation in zebrafish. Meanwhile, the G proteingnai2a, apar1downstream effector, was selectively required for lymphatic development in zebrafish, and its mutation mimicked the lymphatic phenotype observed inpar1mutants. Interestingly, mmp13, but not thrombin, was required for lymphatic development in zebrafish. Furthermore, analyses of genetic interactions confirmed thatmmp13bserves as apar1upstream protease to regulate lymphatic development in zebrafish embryos. Mechanistically,par1promotesflt4expression and phospho-Erk1/2 activity in the posterior cardinal vein. Taken together, our findings highlight a function ofpar1in the regulation of lymphatic differentiation in zebrafish embryos.Graphical abstractDisplay OmittedHighlights•The Mmp13b-Par1-Gnai2a axis regulates lymphatic differentiation in zebrafish•Par1mutant showed decreased prox1a expression in parachordal lymphangioblasts•Par1promotesflt4expression in the posterior cardinal vein of zebrafish embryosBiological sciences; Molecular biology; Immunology
