PUBLICATION

Noncanonical protease-activated receptor 1 regulates lymphatic differentiation in zebrafish

Authors
Lei, D., Zhang, X., Rouf, M.A., Mahendra, Y., Wen, L., Li, Y., Zhang, X., Li, L., Wang, L., Zhang, T., Wang, G., Wang, Y.
ID
ZDB-PUB-211129-9
Date
2021
Source
iScience   24: 103386 (Journal)
Registered Authors
Lei, Daoxi, Li, Li, Wang, Guixue, Wang, Yeqi, Wen, Lin, Zhang, Xiaojuan
Keywords
Biological sciences, Immunology, Molecular biology
MeSH Terms
none
PubMed
34816109 Full text @ iScience
Abstract
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.
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping